Sex differences in left ventricular remodelling, myocardial fibrosis and mortality after aortic valve replacement.

OBJECTIVES: To investigate sex differences in left ventricular remodelling and outcome in patients undergoing surgical or transcatheter aortic valve replacement (SAVR/TAVR). METHODS: In this multicentre, observational, outcome study with imaging core-lab analysis, patients with severe aortic stenosis (AS) listed for intervention at one of six UK centres were prospectively recruited and underwent cardiovascular magnetic resonance imaging. The primary endpoint was all-cause mortality and secondary endpoint was cardiovascular mortality. RESULTS: 674 patients (425 men, 249 women, age 75±14 years) were included: 399 SAVR, 275 TAVR. Women were older, had higher surgical risk scores and underwent TAVR more frequently (53% vs 33.6%, p<0.001). More men had bicuspid aortic valves (BAVs) (26.7% vs 14.9%, p<0.001) and demonstrated more advanced remodelling than women. During a median follow-up of 3.6 years, 145 (21.5%) patients died, with no significant sex difference in all-cause mortality (23.3% vs 20.5%, p=0.114), but higher cardiovascular mortality in women (13.7% vs 8.5%, p=0.012). There were no significant sex-related differences in outcome in the SAVR or TAVR subgroups, or after excluding those with BAV. Factors independently associated with all-cause mortality were age, left ventricular ejection fraction (LVEF), BAV (better) and myocardial fibrosis detected with late gadolinium enhancement (LGE) in men, and age, LVEF and LGE in women. Age and LGE were independently associated with cardiovascular mortality in both sexes. CONCLUSIONS: Men demonstrate more advanced remodelling in response to a similar severity of AS. The higher cardiovascular mortality observed in women following AVR is accounted for by women having less BAV and higher risk scores resulting in more TAVR. LGE is associated with a worse prognosis in both sexes.

Myocardial Scar and Mortality in Severe Aortic Stenosis.

BACKGROUND: Aortic valve replacement (AVR) for aortic stenosis is timed primarily on the development of symptoms, but late surgery can result in irreversible myocardial dysfunction and additional risk. The aim of this study was to determine whether the presence of focal myocardial scar preoperatively was associated with long-term mortality. METHODS: In a longitudinal observational outcome study, survival analysis was performed in patients with severe aortic stenosis listed for valve intervention at 6 UK cardiothoracic centers. Patients underwent preprocedural echocardiography (for valve severity assessment) and cardiovascular magnetic resonance for ventricular volumes, function and scar quantification between January 2003 and May 2015. Myocardial scar was categorized into 3 patterns (none, infarct, or noninfarct patterns) and quantified with the full width at half-maximum method as percentage of the left ventricle. All-cause mortality and cardiovascular mortality were tracked for a minimum of 2 years. RESULTS: Six hundred seventy-four patients with severe aortic stenosis (age, 75±14 years; 63% male; aortic valve area, 0.38±0.14 cm2/m2; mean gradient, 46±18 mm Hg; left ventricular ejection fraction, 61.0±16.7%) were included. Scar was present in 51% (18% infarct pattern, 33% noninfarct). Management was surgical AVR (n=399) or transcatheter AVR (n=275). During follow-up (median, 3.6 years), 145 patients (21.5%) died (52 after surgical AVR, 93 after transcatheter AVR). In multivariable analysis, the factors independently associated with all-cause mortality were age (hazard ratio [HR], 1.50; 95% CI, 1.11-2.04; P=0.009, scaled by epochs of 10 years), Society of Thoracic Surgeons score (HR, 1.12; 95% CI, 1.03-1.22; P=0.007), and scar presence (HR, 2.39; 95% CI, 1.40-4.05; P=0.001). Scar independently predicted all-cause (26.4% versus 12.9%; P<0.001) and cardiovascular (15.0% versus 4.8%; P<0.001) mortality, regardless of intervention (transcatheter AVR, P=0.002; surgical AVR, P=0.026 [all-cause mortality]). Every 1% increase in left ventricular myocardial scar burden was associated with 11% higher all-cause mortality hazard (HR, 1.11; 95% CI, 1.05-1.17; P<0.001) and 8% higher cardiovascular mortality hazard (HR, 1.08; 95% CI, 1.01-1.17; P<0.001). CONCLUSIONS: In patients with severe aortic stenosis, late gadolinium enhancement on cardiovascular magnetic resonance was independently associated with mortality; its presence was associated with a 2-fold higher late mortality.