Jenkins, William

Background: Aortic Valve Calcification (AVC) is intrinsic to aortic stenosis (AS). While established concepts assume homogeneous calcification causing AS, wide variability in hemodynamic severity at any given AVC burden suggests other operative mechanisms. Multidetector computed tomography (MDCT) now accurately measures global AVC, but AVC spatial distribution remains elusive due to imaging orientation. Methods and Results: We developed ‘en-face’ imaging by re-registration of 4D-MDCT to quantify AVC spatial distribution and analyzed global AVC load and AVC distribution in 418 patients with AS (76±9 years; mean gradient 35±17 mmHg). 4D-volume-rendered MDCT datasets were re-oriented to en-face view of aortic valve for AVC spatial scoring with individual cusp calcification load, cusp-edge calcification and AVC asymmetry. Despite high total AVC load (450 [250-666] AU/cm 2 ), asymmetry was frequent (50%), with a difference between most- and least-calcified cusp of 112 [66-182] AU/cm 2 . Maximum AVC was in the non-coronary cusp in 61% (p<0.001). Cusp edge calcification was none-mild in 26%, moderate in 62% and severe in 12%. Adjusting for total AVC, severe AS (mean gradient >40 mmHg) was more likely with symmetrical AVC (odds ratio [OR] 2.36, p<0.001) and with edge calcification moderate (OR 4.16, p=0.001 vs none-mild) to severe (OR 10.7, p=0.001). Inclusion of AVC distribution improved models predicting AS severity over total AVC (p<0.001). Conclusions: Four-dimensional MDCT en-face re-registration and AVC quantitation provides new insight into AS pathophysiology. Contrary to classical concepts, AVC is frequently inhomogeneous and asymmetric. Hemodynamic AS severity is independently affected not only by global AVC but also by variations in AVC distribution and location within cusps, emphasizing the importance of 4D AVC assessment in AS. Impact of quantified AVC asymmetry and location on outcome of transcutaneous aortic valve replacement should be evaluated.

Introduction: Soluble ST2 (sST2) is a serum marker of cardiomyocyte stress associated with a large risk of death and heart failure after myocardial infarction (MI). The relationship between sST2 and cardiac structure and function after MI however remains incompletely defined, and greater characterization is required prior to clinical application. Methods: Olmsted County, Minnesota residents who experienced their first MI between 2007 and 2012 were prospectively recruited. MIs were validated using standardized criteria and patients underwent simultaneous comprehensive Doppler echocardiography and sST2 measurement. The association between cardiac morphology and hemodynamics and sST2 were examined. Published normal values were used as referent ranges for sST2 levels. Results: Among 316 patients (mean age 65 [SD 14] years, 67% men, 32% ST-elevation MI), sST2 was measured 2.5 [SD 1.6] days after MI and within 0.7 [SD 2.3] days of echocardiography. Soluble ST2 was elevated in 33% of patients and univariately associated with decreased LV ejection fraction (LVEF), increased LV mass, impaired LV diastolic function and increased pulmonary artery pressure (ePAP) (Table). After adjustment for age, sex, LVEF and key measures of LV filling pressures, elevated sST2 was independently associated with reduced LVEF (p=0.01) mitral valve deceleration time (p=0.03), greater left atrial volume (p=0.03) and mitral regurgitation (≥mild; p=0.09). LVEF and ePAP exhibited the strongest associations with elevated sST2 (both p<0.001). Conclusions: Soluble ST2 is frequently elevated following MI and is strongly associated with the morphologic and hemodynamic determinants of adverse LV remodeling that infer poor long-term outcome after MI.