Rudbæk, Torsten R

Background Plasma fibulin‐1 levels have been associated with N‐terminal pro–B‐type natriuretic peptide levels and left atrial size and shown to be predictive of mortality in patients with diabetes. The mechanisms behind these connections are not fully understood but are probably related to its roles as an extracellular matrix protein in cardiovascular tissues. Methods and Results One hundred twenty‐five patients with severe aortic stenosis who were scheduled for aortic valve replacement ( AVR ) were evaluated with preoperative echocardiography and their plasma fibulin‐1 levels were determined with ELISA . The cohort was followed for a median of 4 years after AVR . Increased restrictive left ventricular ( LV ) filling pattern was observed with increased plasma fibulin‐1 levels (2% versus 29% versus 24% in low, middle, and high plasma fibulin‐1 tertile groups, P =0.004). Likewise, reduced longitudinal systolic LV function (6.6±1.1 versus 6.1±1.3 versus 5.7±1.5 cm/s, P =0.05) and increased LV filling pressures was systolic velocity of the mitral annulus observed with increasing plasma fibulin‐1 concentrations (ratio of early transmitral flow velocity to early diastolic flow velocity of the mitral annulus 13±4 versus 15±5 versus 16±6 in the fibulin‐1 tertile groups, P =0.04). Conclusions In patients with symptomatic severe aortic stenosis undergoing AVR, plasma fibulin‐1 is associated with restrictive filling of the LV , decreased longitudinal systolic function of the LV , and increased LV filling pressures. Clinical Trial Registration URL: www.clinicaltrial.gov with Identifier: NCT00294775

Background— Global longitudinal systolic strain (GLS) is often reduced in aortic stenosis despite normal ejection fraction. The importance of reduced preoperative GLS on long-term outcome after aortic valve replacement is unknown. Methods and Results— A total of 125 patients with severe aortic stenosis and ejection fraction >40% scheduled for aortic valve replacement were evaluated preoperatively and divided into 4 groups according to GLS quartiles. Patients were followed up for 4 years. The primary end points were major adverse cardiac events (MACEs) defined as cardiovascular mortality and cardiac hospitalization because of worsening of heart failure; the secondary end point was cardiovascular mortality. MACE and cardiac mortality were significantly increased in patients with lower GLS. Estimated 5-year MACE was increased: first quartile 19% (n=6) / second quartile 20% (n=6) / third quartile 35% (n=11) / fourth quartile 49% (n=15); P =0.04. Patients with increased age, left ventricular hypertrophy, and left atrial dilatation were at increased risk. In Cox regression analysis, after correcting for standard risk factors and ejection fraction, GLS was found to be significantly associated with cardiac morbidity and mortality. In a stepwise Cox model with forward selection, GLS was the sole independent predictor: hazard ratio=1.13 (95% confidence interval, 1.02–1.25), P =0.04. Comparing the overall log likelihood χ 2 of the predictive power of the multivariable model containing GLS was statistically superior to models based on EuroScore, history with ischemic heart disease, and ejection fraction. Conclusions— In patients with symptomatic severe aortic stenosis undergoing aortic valve replacement, reduced GLS provides important prognostic information beyond standard risk factors. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00294775.