Anne Ringle

Prognostic Value of Aortic Valve Area by Doppler Echocardiography in Patients With Severe Asymptomatic Aortic Stenosis

Background The aim of this study was to evaluate the relationship between aortic valve area (AVA) obtained by Doppler echocardiography and outcome in patients with severe asymptomatic aortic stenosis and to define a specific threshold of AVA for identifying asymptomatic patients at very high risk based on their clinical outcome. Methods and Results We included 199 patients with asymptomatic severe aortic stenosis (AVA ≤1.0 cm2). The risk of events (death or need for aortic valve replacement) increased linearly on the scale of log hazard with decreased AVA (adjusted hazard ratio 1.17; 95% CI 1.06–1.29 per 0.1 cm2 AVA decrement; P=0.002). Event‐free survival at 12, 24, and 48 months was 63±6%, 51±6%, and 34±6%, respectively, for AVA 0.8 to 1 cm2; 49±6%, 36±6%, and 26±6%, respectively, for AVA 0.6 to 0.8 cm2; and 33±8%, 20±7%, and 11±5%, respectively, for AVA ≤0.6 cm2 (P trend=0.002). Patients with AVA ≤0.6 cm2 had a significantly increased risk of events compared with patients with AVA 0.8 to 1 cm2 (adjusted hazard ratio 2.22; 95% CI 1.41–3.52; P=0.001), whereas patients with AVA 0.6 to 0.8 cm2 had an increased risk of events compared with those with AVA 0.8 to 1 cm2, but the difference was not statistically significant (adjusted hazard ratio 1.38; 95% CI 0.93–2.05; P=0.11). After adjustment for covariates and aortic valve replacement as a time‐dependent variable, patients with AVA ≤0.6 cm2 had a significantly greater risk of all‐cause mortality than patients with AVA >0.6 cm2 (hazard ratio 3.39; 95% CI 1.80–6.40; P<0.0001). Conclusions Patients with severe asymptomatic aortic stenosis and AVA ≤0.6 cm2 displayed an important increase in the risk of adverse events during short‐term follow‐up. Further studies are needed to determine whether elective aortic valve replacement improves outcome in this high‐risk subgroup of patients.

Impact of pulmonary hypertension on long-term outcome in patients with severe aortic stenosis

Aims Pulmonary hypertension (PH) is common in severe symptomatic left-sided valvular disease, particularly in aging populations. Inconsistent results have been reported concerning the association between PH and adverse outcomes after aortic valve replacement for aortic stenosis (AS). We therefore retrospectively investigated the prognostic significance of PH using peak tricuspid regurgitation velocity (TRV), as defined by the current European Society of Cardiology (ESC)/European Respiratory Society (ERS) guidelines, in a large cohort of patients with severe AS. Methods and results One thousand and nineteen patients (541 men; mean age 74 ± 11 years) with severe AS (aortic valve area (AVA) <1 cm2 and/or indexed AVA <0.6 cm2/m2 of body surface area) and LV ejection fraction ≥50% were included. Patients were divided into three groups according to the level of their peak TRV at the time of enrolment: Group 1 (n = 695, 68%) when TRV was ≤2.8 m/s; Group 2 (n = 212, 21%) when TRV was between 2.9 m/s and 3.4 m/s and Group 3 (n = 112, 11%) when TRV was > 3.4 m/s. Median overall follow-up was 31 [6-182] months. On univariate analysis, overall mortality during follow-up was globally different between groups (P < 0.001). On multivariate analysis, Group 3 (TRV >3.4 m/s) exhibited significant excess mortality after adjustment for covariates of prognostic importance (P = 0.032) and after further adjustment for surgery (P = 0.012), using Group 1 as the reference group. Dividing the whole population into two groups with a 3.4 m/s TRV threshold, overall mortality during follow-up was higher in the PH group [hazard ratio (HR) 1.87; 95% confidence interval [1.37-2.56]; P < 0.001)]. On multivariate analysis, after covariate adjustment, including surgery, Group 3 exhibited major excess mortality (adjusted HR 1.46 [1.10-1.95], P = 0.009). Conclusion This study demonstrates the negative impact of pulmonary pressure, as assessed by current ESC/ERS guidelines, on long-term outcome of patients with severe AS, irrespective of functional status, chronic obstructive pulmonary disease, AS severity and surgery. Baseline TRV should therefore be taken into account in the management of severe AS.

Impact of low stroke volume on mortality in patients with severe aortic stenosis and preserved left ventricular ejection fraction

Aims In patients with severe aortic stenosis (AS) and preserved left ventricular ejection fraction (LVEF), low flow (LF) is currently defined using Doppler-echocardiography by a stroke volume index (SVi)<35 mL/m2. However, the relationship between LF and outcome remains unclear as data on normal reference values defining LF are scarce, and previous studies did not explore the risk associated with other SVi cut-points. We analysed the relationship between LF and mortality in severe AS to establish prognostic LF values associated with mortality risk. Methods and results This study included 1450 consecutive patients with severe AS (aortic valve area <1 cm2 and/or <0.6 cm2/m2) and preserved LVEF and 1645 controls with normal echocardiograms. Patients were stratified in three groups: (i) SVi > 35 mL/m2 or SV > 70 mL; (ii) SVi 30-35 mL/m2 or SV 55-70 mL; and (iii) SVi < 30 mL/m2 or SV < 55 mL. Mortality with medical and surgical management was analysed. Five-year survival was low for SVi < 30 mL/m2 and SV < 55 mL compared to the other groups (all P-values <0.001). After adjustment for outcome predictors, including aortic valve replacement, mortality risk was considerable with SVi < 30 mL/m2 vs. >35 mL/m2 [adjusted hazard ratio (HR) 1.60 (1.17-2.18)] and SV < 55 mL vs. >70 mL [adjusted HR 1.84 (1.32-2.58)]. Similar mortality risk was observed for SVi 30-35 mL/m2 vs. >35 mL/m2 [adjusted HR 1.05 (0.78-1.41)], and for SV 55-70 mL vs. >70 mL [adjusted HR 1.22 (0.94-1.58)]. The prognostic impact of SVi < 30 mL/m2 and SV < 55 mL was consistent in subgroups, including asymptomatic patients and patients with low-gradient severe AS. Conclusion Low flow defined as SVi < 30 mL/m2 or SV < 55 mL is an important outcome predictor in severe AS with preserved LVEF under medical and surgical management. Further studies are needed to prospectively test these values for risk stratification and decision making.

Impact of Mean Transaortic Pressure Gradient on Long‐Term Outcome in Patients With Severe Aortic Stenosis and Preserved Left Ventricular Ejection Fraction

Background Mean transaortic pressure gradient (MTPG) has never been validated as a predictor of mortality in patients with severe aortic stenosis. We sought to determine the value of MTPG to predict mortality in a large prospective cohort of severe aortic stenosis patients with preserved left ventricular ejection fraction and to investigate the cutoff of 60 mm Hg, proposed in American guidelines. Methods and Results A total of 1143 patients with severe aortic stenosis defined by aortic valve area ≤1 cm2 and MTPG ≥40 mm Hg were included. The population was divided into 3 groups according to MTPG: between 40 and 49 mm Hg, between 50 and 59 mm Hg, and ≥60 mm Hg. The end point was all‐cause mortality. MTPG was ≥60 mm Hg in 392 patients. Patients with MTPG ≥60 mm Hg had a significantly increase risk of mortality compared with patients with MTPG <60 mm Hg (hazard ratio [HR]=1.62 [1.27–2.05] P<0.001), even for the subgroup of asymptomatic or minimally symptomatic patients (HR=1.56 [1.04–2.34] P=0.032). After adjustment for established outcome predictors, patients with MTPG ≥60 mm Hg had a significantly higher risk of mortality than patients with MTPG <60 mm Hg (HR=1.71 [1.33–2.20] P<0.001), even after adjusting for surgery as a time‐dependent variable (HR=1.71 [1.43–2.11] P<0.001). Similar results were observed for the subgroup of asymptomatic or minimally symptomatic patients (HR=1.70 [1.10–2.32] P=0.018 and HR=1.68 [1.20–2.36] P=0.003, respectively). Conclusions This study shows the negative prognostic impact of high MTPG (≥60 mm Hg), on long‐term outcome of patients with severe aortic stenosis with preserved left ventricular ejection fraction, irrespective of symptoms.

Correction: Asymptomatic aortic stenosis: An assessment of patients' and of their general practitioners' knowledge, after an indexed specialized assessment in community practice

[This corrects the article DOI: 10.1371/journal.pone.0179988.].

Left Atrial Volume and Mortality in Patients With Aortic Stenosis

Background Left atrium (LA) enlargement is common in patients with aortic stenosis (AS), yet its prognostic implications are unclear. This study investigates the value of left atrial volume (LAV) and LAV normalized to body size for predicting mortality in AS. Methods and Results We included 1351 patients with AS in sinus rhythm at diagnosis and analyzed the occurrence of all‐cause death during follow‐up with medical and surgical management. Five parameters of LA enlargement were tested: nonindexed LAV and normalized LAV by ratiometric (LAV/body surface area [BSA] and LAV/height) and allometric (LAV/BSA 1.7 and LAV/height2.0) scaling. For each parameter, patients in the highest quartile were at high risk of death, whereas outcome was better and similar for the other quartiles. Five‐year survival was lower for patients with LAV >95 mL and LAV/BSA >50 mL/m2 compared with those with no or mild LA enlargement (both P<0.001). After adjustment for established outcome predictors, including surgery, high risk of death was observed with LAV >95 mL (adjusted hazard ratio, 1.40 [95% confidence interval, 1.06–1.88]) and LAV/BSA >50 mL/m2 (adjusted hazard ratio, 1.42 [95% confidence interval, 1.08–1.91]). LAV/BSA and LAV showed good and similar predictive performance, whereas other scaling methods did not show better outcome prediction. In patients with severe AS at baseline, preserved (≥50%) ejection fraction, and no or minimal symptoms, LA enlargement was significantly associated with mortality (adjusted hazard ratio, 1.87 [95% confidence interval, 1.02–3.44] for LAV >95 mL, and adjusted hazard ratio, 1.90 [95% confidence interval, 1.03–3.56] for LAV/BSA >50 mL/m2). Conclusions LA enlargement is an important predictor of mortality in AS, incrementally to known predictors of outcome. LAV and LAV/BSA have comparable predictive performance and should be assessed in clinical practice for risk stratification.

Relationship between exercise pressure gradient and haemodynamic progression of aortic stenosis

BACKGROUND AND AIMS We hypothesized that large exercise-induced increases in aortic mean pressure gradient can predict haemodynamic progression during follow-up in asymptomatic patients with aortic stenosis. METHODS We retrospectively identified patients with asymptomatic moderate or severe aortic stenosis (aortic valve area<1.5cm2 or<1cm2) and normal ejection fraction, who underwent an exercise stress echocardiography at baseline with a normal exercise test and a resting echocardiography during follow-up. The relationship between exercise-induced increase in aortic mean pressure gradient and annualised changes in resting mean pressure gradient during follow-up was investigated. RESULTS Fifty-five patients (mean age 66±15 years; 45% severe aortic stenosis) were included. Aortic mean pressure gradient significantly increased from rest to peak exercise (P<0.001). During a median follow-up of 1.6 [1.1-3.2] years, resting mean pressure gradient increased from 35±13mmHg to 48±16mmHg, P<0.0001. Median annualised change in resting mean pressure gradient during follow-up was 5 [2-11] mmHg. Exercise-induced increase in aortic mean pressure gradient did correlate with annualised changes in mean pressure gradient during follow-up (r=0.35, P=0.01). Hemodynamic progression of aortic stenosis was faster in patients with large exercise-induced increase in aortic mean pressure gradient (≥20mmHg) as compared to those with exercise-induced increase in aortic mean pressure gradient<20mmHg (median annualised increase in mean pressure gradient 19 [6-28] vs. 4 [2-10] mmHg/y respectively, P=0.002). Similar results were found in the subgroup of 30 patients with moderate aortic stenosis. CONCLUSION Large exercise-induced increases in aortic mean pressure gradient correlate with haemodynamic progression of stenosis during follow-up in patients with asymptomatic aortic stenosis. Further studies are needed to fully establish the role of ESE in the decision-making process in comparison to other prognostic markers in asymptomatic patients with aortic stenosis.