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Marfan syndrome (MFS) is an autosomal-dominant disorder of connective tissue caused by mutations in the fibrillin-1 (FBN1) gene. Mortality is often due to aortic dissection and rupture. We investigated the structural and functional properties of the heart and aorta in a [Fbn1C1039G/+] MFS mouse using high-resolution ultrasound (echo) and optical coherence tomography (OCT). Echo was performed on 6- and 12-month old wild type (WT) and MFS mice (n = 8). In vivo pulse wave velocity (PWV), aortic root diameter, ejection fraction, stroke volume, left ventricular (LV) wall thickness, LV mass and mitral valve early and atrial velocities (E/A) ratio were measured by high resolution echocardiography. OCT was performed on 12-month old WT and MFS fixed mouse hearts to measure ventricular volume and mass. The PWV was significantly increased in 6-mo MFS vs. WT (366.6 ± 19.9 vs. 205.2 ± 18.1 cm/s; p = 0.003) and 12-mo MFS vs. WT (459.5 ± 42.3 vs. 205.3 ± 30.3 cm/s; p< 0.0001). PWV increased with age in MFS mice only. We also found a significantly enlarged aortic root and decreased E/A ratio in MFS mice compared with WT for both age groups. The [Fbn1C1039G/+] mouse model of MFS replicates many of the anomalies of Marfan patients including significant aortic dilation, central aortic stiffness, LV systolic and diastolic dysfunction. This is the first demonstration of the direct measurement in vivo of pulse wave velocity non-invasively in the aortic arch of MFS mice, a robust measure of aortic stiffness and a critical clinical parameter for the assessment of pathology in the Marfan syndrome.

Fifty patients with a mean age of 9.2 years (range, 1.2 to 17.5 years) had cardiac catheterization performed under standardized conditions plus a scalar ECG the previous day. Twenty different direct measurements and 25 derived measurements from the ECG were correlated with the resting peak systolic gradient across the aortic valve. Some of the best correlations were with the measured TAVF, TV6, QV6, and the sum of SV1 + RV6 with r values between .33 and .59. Another group of different patients with isolated aortic stenosis were studied with measurements of the important ECG segments. The r value of this "test" series was similar to that of the original group, so the groups were pooled. The best three-term regression equation involved TAVF, QV6, and the sum (SV1 + RV6), with r = .636. A scoring system was also devised to predict severity. If the TAVF is 0.1 mV or less or the TV6 is 0.3 mV or less or if there is no Q in V6, the gradient may be high. In our series, the ECG estimation of resting peak systolic gradient across the aortic valve in aortic stenosis was enhanced by the inclusion of TAVF and QV6 in the regression equation, as well as SV1 + RV6.