Aortic root 3D parametric morphological model from 2D-echo images

The gold standard for the study of the macro-anatomy of the aortic root are multi-detector computed tomography (MDCT) and magnetic resonance (MR) imaging. Both technologies have major advantages and limitations. Although 4D echo is entering the study of the aortic root, 2D echo is the most commonly used diagnostic tool in daily practice. We designed and developed an algorithm for 3D modeling of the aortic root based on measures taken routinely at 2D echocardiography from 20 healthy individuals with normal aortic root. The tool was then translated in 12 patients who underwent both echo and MDCT. The results obtained with the 3D modeling program were quantitatively and qualitatively compared with 3D reconstruction from MDCT. Ad hoc ratios describing the morphology of the aortic root in MDCT and in the 3D model were used for comparison. In 12 patients with aortic root dilatation, the ratios obtained with our model are in good agreement with those from MDCT. Linear correlation for both long axis and short axis ratios was strong. The 3D modeling software can be easily adopted by cardiologists routinely involved in clinical evaluation of the pathology of the aortic root. The tool is easy to apply, does not require additional costs, and may be used to generate a set of data images for monitoring the evolution of the morphology and dimension of the aortic root, flanking the 3D MDCT and MR that remain the gold standard tool

Diagnostic work-up and risk stratification in X-linked dilated cardiomyopathies caused by dystrophin defects

OBJECTIVES: We sought to describe the diagnostic work-up, phenotype, and long-term evolution of dilated cardiomyopathy (DCM) associated with Dystrophin (DYS) defects. BACKGROUND: X-linked DCM associated with DYS defects can be clinically indistinguishable from other types of DCM. METHODS: The series comprises 436 consecutive male patients diagnosed with DCM. Patients underwent endomyocardial biopsy (EMB). Genetic testing employed multiplex polymerase chain reaction and multiple ligation dependent probe assay for deletions and direct sequencing of the 79 exons and flanking regions of the gene for point mutations or small rearrangements. RESULTS: We identified DYS defects in 34 of 436 patients (7.8%) (onset age 34 ± 11 years, age range 17 to 54 years); 30 had proven X-linked inheritance. The 2 phenotypes included DCM with mild skeletal myopathy and/or increased serum creatine phosphokinase (n = 28) or DCM only (n = 6). The EMB showed defective dystrophin immunostain. The DYS defects consisted of 21 in-frame deletions and 11 out-of-frame deletions as well as 1 stop and 1 splice-site mutation. During a median follow-up of 60 months (interquartile range: 11.25 to 101.34 months) we observed 17 events, all related to heart failure (HF) (median event-free survival: 83.5 months). Eight patients (23%) underwent transplantation, and 9 (26%) died of HF while waiting for transplantation. Eight patients received an implantable cardioverter-defibrillator, although none had device intervention during a median follow-up of 14 months (interquartile range: 5 to 25 months). No patient died suddenly, suffered syncope, or developed life-threatening ventricular arrhythmias. CONCLUSIONS: DYS-related DCM should be suspected in male patients with increased serum creatine phosphokinase (82%) and X-linked inheritance. The disease shows a high risk of end-stage HF but a lower risk of life-threatening arrhythmias

Quantitative expression of the mutated lamin A/C gene in patients with cardiolaminopathy.

OBJECTIVES: The authors sought to investigate the gene and protein expression in Lamin A/C (LMNA)-mutated dilated cardiolaminopathy (DCM) patients (DCM(LMNAMut)) versus LMNA-wild-type DCM (DCM(LMNAWT)), and normal controls (CTRL(LMNAWT)). BACKGROUND: Dilated cardiolaminopathies are clinically characterized by high arrhythmogenic risk and caused by LMNA mutations. Little is known regarding quantitative gene expression (QGE) of the LMNA gene in blood and myocardium, as well as regarding myocardial expression of the lamin A/C protein. METHODS: Using the comparative ΔΔCT method, we evaluated the QGE of LMNA (QGE(LMNA)) in peripheral blood and myocardial RNA from carriers of LMNA mutations, versus blood and myocardial samples from DCM(LMNAWT) patients and CTRL(LMNAWT) individuals. After generating reference values in normal controls, QGE(LMNA) was performed in 311 consecutive patients and relatives, blind to genotype, to assess the predictive value of QGE(LMNA) for the identification of mutation carriers. In parallel, Lamin A/C was investigated in myocardial samples from DCM(LMNAMut) versus DCM(LMNAWT) versus normal hearts (CTRL(LMNAWT)). RESULTS: LMNA was significantly underexpressed in mRNA from peripheral blood and myocardium of DCM(LMNAMut) patients versus DCM(LMNAWT) and CTRL(LMNAWT). In 311 individuals, blind to genotype, the QGE(LMNA) showed 100% sensitivity and 87% specificity as a predictor of LMNA mutations. The receiver-operating characteristic curve analysis yielded an area under the curve of 0.957 (p < 0.001). Loss of protein in cardiomyocytes' nuclei was documented in DCM(LMNAMut) patients. CONCLUSIONS: The reduced expression of LMNA gene in blood is a novel potential predictive biomarker for dilated cardiolaminopathies with parallel loss of protein expression in cardiomyocyte nuclei