Prognosis and follow-up of patients with prosthetic valve endocarditis treated conservatively in relation to WBC-SPECT imaging.

BACKGROUND: Our objective was to evaluate in patients with prosthetic valve endocarditis (PVE) treated conservatively, the prognostic value of white blood cell (WBC) signal intensity on SPECT and to describe the evolution of the WBC signal under antibiotics. METHODS: Patients with PVE treated conservatively and positive WBC-SPECT imaging were identified retrospectively. Signal intensity was classified as intense if equal to or higher, or mild if lower, than the liver signal. Clinical, biological, imaging and follow-up information were collected from medical files. RESULTS: Among 47 patients, WBC signal was classified as intense in 10 patients and as mild, in 37. The incidence of the primary composite endpoint (death, late cardiac surgery, or relapse) was significantly higher in patients with intense vs. mild signal (90% vs. 11%). Twenty-five patients underwent a second WBC-SPECT imaging during follow-up. The prevalence of WBC signal decreased progressively from 89% between 3 and 6 weeks to 42% between 6 and 9 weeks and 8% more than 9 weeks after initiation of antibiotics. CONCLUSIONS: In patients with PVE treated conservatively, intense WBC signal was associated with poor outcome. WBC-SPECT imaging appears as an interesting tool for risk stratification and to monitor locally the efficacy of antibiotic treatment.

Cerebrovascular complications and outcomes of critically ill adult patients with infective endocarditis.

BACKGROUND: Neurological complications are associated with poor outcome in patients with infective endocarditis (IE). Although guidelines recommend systematic brain imaging in the evaluation of IE patients, the association between early brain imaging findings and outcomes has never been evaluated in critically ill patients. We aimed to assess the association of CT-defined neurological complications with functional outcomes of critically ill IE patients. METHODS: This retrospective cohort study included consecutive patients with severe, left-sided IE hospitalized in the medical ICU of a tertiary care hospital. Patients with no baseline brain CT were excluded. Baseline CT-scans were classified in five mutually exclusive categories (normal, moderate-to-severe ischemic stroke, minor ischemic stroke, intracranial hemorrhage, other abnormal CT). The primary endpoint was 1-year favorable outcome, defined by a modified Rankin Scale score of 0-3. RESULTS: Between 06/01/2011 and 07/31/2018, 156 patients were included. Among them, 87/156 (56%) had a CT-defined neurological complication, including moderate-to-severe ischemic stroke (n = 33/156, 21%), intracranial hemorrhage (n = 24/156, 15%), minor ischemic stroke (n = 29/156, 19%), other (n = 3/156, 2%). At one year, 69 (45%) patients had a favorable outcome. Factors negatively associated with favorable outcome in multivariable analysis were moderate-to-severe ischemic stroke (OR 0.37, 95%CI 0.14 - 0.95) and age (OR 0.94, 95%CI 0.91-0.97). By contrast, the score on the Glasgow Coma Scale was positively associated with favorable outcome (per 1-point increment, OR 1.23, 95%CI 1.08-1.42). Sensitivity analyses conducted in operated patients revealed similar findings. Compared to normal CT, only moderate-to-severe ischemic stroke was associated with more frequent post-operative neurological complications (n = 8/23 (35%) vs n = 1/46 (2%), p < 0.01). CONCLUSION: Moderate-to-severe ischemic stroke had an independent negative impact on 1-year functional outcome in critically ill IE patients; whereas other complications, including intracranial hemorrhage, had no such impact.

Diagnostic performance of White Blood Cell SPECT imaging against intra-operative findings in patients with a suspicion of prosthetic valve endocarditis.

AIM: The objective of this study was to evaluate the diagnostic performance of white blood cells (WBC)-SPECT imaging in patients with suspicion of prosthetic valve endocarditis (PVE) against intra-operative findings. METHODS: 36 consecutive patients who underwent cardiac surgery 30 days after WBC-SPECT imaging were identified retrospectively. Clinical, imaging, and biological results were collected from reports. WBC-SPECT results were classified as positive or negative and, if positive, the intensity of signal graded as intense or mild. Lesions observed during cardiac surgery were collected from surgeons' reports. RESULTS: The 20 patients with positive WBC-SPECT study had confirmed PVE intra-operatively. Patients with intense signal on WBC-SPECT had high prevalence of abscesses (83%) compared to patients with only mild signal (12%). The three patients with negative WBC-SPECT but confirmed PVE had longer duration of antibiotic treatment before imaging and had no perivalvular abscess. Sensitivity, specificity, positive predictive and negative values, and accuracy of WBC-SPECT were measured at 87%, 100%, 100%, 81%, and 92%, respectively. Addition of WBC-SPECT results to the modified Duke score helped re-classify correctly 25% of patients from possible to definite PVE. CONCLUSION: In patients with suspicion of PVE, WBC-SPECT imaging provides excellent diagnostic performance against intra-operative findings.

Prognostic Value of Peak Exercise Systolic Pulmonary Arterial Pressure in Asymptomatic Primary Mitral Valve Regurgitation.

BACKGROUND: The contribution of exercise echocardiography in primary asymptomatic mitral regurgitation (MR) remains debated. The aim of this study was to gain evidence regarding its usefulness in this setting and to investigate the prognostic value of peak exercise systolic pulmonary artery pressure (SPAP). METHODS: One hundred seventy-seven patients (mean age, 56 ± 13 years; 69% men) with moderate to severe (grade 3+) or severe (grade 4+) degenerative MR and preserved left ventricular ejection fraction, in sinus rhythm, referred for clinically indicated exercise echocardiography were identified. The end point, MR-related events, was a composite of all-cause death or occurrence of symptoms, heart failure, atrial fibrillation, left ventricular ejection fraction < 60%, left ventricular end-systolic diameter ≥ 45 mm, or resting SPAP > 50 mm Hg. RESULTS: At rest, effective regurgitant orifice area was 48 ± 16 mm2, regurgitant volume 74 ± 26 mL, and SPAP 32 ± 7 mm Hg, and MR was severe in 138 patients (78%). Peak exercise SPAP was 55 ± 10 mm Hg. Positive results on exercise testing motivated surgery in 26 patients, 11 underwent prophylactic surgery, 10 were lost to follow-up, and 130 were included in the outcome analysis. During a follow-up period of 19 ± 7 months, 31 MR-related events (24%) were reported. Peak exercise SPAP was predictive of outcomes in univariate analysis (P = .01) and after adjustment for age, gender, MR severity, and resting SPAP (P < .05). Peak exercise SPAP ≥ 50 mm Hg was associated with worse event-free survival (hazard ratio, 5.24; 95% CI, 1.77-15.53; P = .003), but not the threshold of ≥60 mm Hg proposed in previous guidelines (hazard ratio, 1.70; 95% CI, 0.71-4.03; P = .24). CONCLUSIONS: The present findings support the use of exercise echocardiography for risk stratification in patients with asymptomatic primary MR and suggest a lower peak exercise SPAP threshold (50 mm Hg) than previously recommended to define the timing of intervention. Prospective studies are needed to confirm these findings.

Clinical manifestations and outcomes of coronavirus disease-19 in heart transplant recipients: a multicentre case series with a systematic review and meta-analysis.

Available data on clinical presentation and mortality of coronavirus disease-2019 (COVID-19) in heart transplant (HT) recipients remain limited. We report a case series of laboratory-confirmed COVID-19 in 39 HT recipients from 3 French heart transplant centres (mean age 54.4 ± 14.8 years; 66.7% males). Hospital admission was required for 35 (89.7%) cases including 14/39 (35.9%) cases being admitted in intensive care unit. Immunosuppressive medications were reduced or discontinued in 74.4% of the patients. After a median follow-up of 54 (19-80) days, death and death or need for mechanical ventilation occurred in 25.6% and 33.3% of patients, respectively. Elevated C-reactive protein and lung involvement ≥50% on chest computed tomography (CT) at admission were associated with an increased risk of death or need for mechanical ventilation. Mortality rate from March to June in the entire 3-centre HT recipient cohort was 56% higher in 2020 compared to the time-matched 2019 cohort (2% vs. 1.28%, P = 0.15). In a meta-analysis including 4 studies, pre-existing diabetes mellitus (OR 3.60, 95% CI 1.43-9.06, I2  = 0%, P = 0.006) and chronic kidney disease stage III or higher (OR 3.79, 95% CI 1.39-10.31, I2  = 0%, P = 0.009) were associated with increased mortality. These findings highlight the aggressive clinical course of COVID-19 in HT recipients.

Size-adjusted aortic valve area: refining the definition of severe aortic stenosis.

AIMS: Severe aortic valve stenosis (AS) is defined by an aortic valve area (AVA) <1 cm2 or an AVA indexed to body surface area (BSA) <0.6 cm/m2, despite little evidence supporting the latter approach and important intrinsic limitations of BSA indexation. We hypothesized that AVA indexed to height (H) might be more applicable to a wide range of populations and body morphologies and might provide a better predictive accuracy. METHODS AND RESULTS: In 1298 patients with degenerative AS and preserved ejection fraction from three different countries and continents (derivation cohort), we aimed to establish an AVA/H threshold that would be equivalent to 1.0 cm2 for defining severe AS. In a distinct prospective validation cohort of 395 patients, we compared the predictive accuracy of AVA/BSA and AVA/H. Correlations between AVA and AVA/BSA or AVA/H were excellent (all R2 > 0.79) but greater with AVA/H. Regressions lines were markedly different in obese and non-obese patients with AVA/BSA (P < 0.0001) but almost identical with AVA/H (P = 0.16). AVA/BSA values that corresponded to an AVA of 1.0 cm2 were markedly different in obese and non-obese patients (0.48 and 0.59 cm2/m2) but not with AVA/H (0.61 cm2/m for both). Agreement for the diagnosis of severe AS (AVA < 1 cm2) was significantly higher with AVA/H than with AVA/BSA (P < 0.05). Similar results were observed across the three countries. An AVA/H cut-off value of 0.6 cm2/m [HR = 8.2(5.6-12.1)] provided the best predictive value for the occurrence of AS-related events [absolute AVA of 1 cm2: HR = 7.3(5.0-10.7); AVA/BSA of 0.6 cm2/m2 HR = 6.7(4.4-10.0)]. CONCLUSION: In a large multinational/multiracial cohort, AVA/H was better correlated with AVA than AVA/BSA and a cut-off value of 0.6 cm2/m provided a better diagnostic and prognostic value than 0.6 cm2/m2. Our results suggest that severe AS should be defined as an AVA < 1 cm2 or an AVA/H < 0.6 cm2/m rather than a BSA-indexed value of 0.6 cm2/m2.

Epicardial adipose tissue volume is associated with left ventricular remodelling in calcific aortic valve stenosis.

BACKGROUND: The severity of left ventricular (LV) remodelling is only partially related to the severity of aortic valve stenosis; additional factors, including diabetes, insulin resistance, obesity and metabolic syndrome, may play important roles. Epicardial adipose tissue (EAT), now considered as a metabolically active organ, is also linked to these factors. AIM: To analyse the association between EAT volume measured using computed tomography and LV remodelling in a prospective cohort of patients with aortic stenosis. METHODS: Consecutive asymptomatic patients with at least mild degenerative aortic stenosis enrolled in a prospective cohort that aimed to assess the determinants of aortic stenosis occurrence and progression constituted our population. RESULTS: We enrolled 143 patients (78±5 years; 65% men). Mean LV mass and EAT volume were 219±64g and 134±56mL, respectively. LV hypertrophy was diagnosed in 86 patients (60%), and concentric hypertrophy (32%) was the main remodelling pattern. EAT was associated with body mass index (P<0.001) and body surface area (P<0.001), but not with age (P=0.33) or aortic stenosis severity (all P>0.10). EAT was correlated with LV mass (r=0.41; P<0.0001), and after adjustment for age, sex, body mass index/body surface area, hypertension, waist circumference, low-density lipoprotein cholesterol and aortic stenosis severity, EAT was independently associated with LV mass (P=0.01/P=0.02). Similar results were found when EAT and LV mass index (adjusted for body surface area) were considered instead of absolute values (P=0.04). CONCLUSIONS: In this prospective cohort of patients with aortic stenosis, EAT volume was independently associated with LV mass. Further studies are warranted to elucidate the underlying mechanisms of this link.

Systematic transoesophageal echocardiography after mitral valve replacement: Rates and determinants of paravalvular regurgitation.

BACKGROUND: With the emergence of transcatheter mitral valve replacement, it appears crucial to provide contemporary references with which this new technology can be compared. At our institution, transoesophageal echocardiography is systematically performed before discharge after surgical mitral valve replacement. AIM: To evaluate the rate and determinants of paravalvular regurgitation after surgical mitral valve replacement. METHODS: We collected medical history, indication, type of surgery and in-hospital outcome in all consecutive patients who underwent a mitral valve replacement in the past 2 years at our institution. Paravalvular regurgitation was assessed semiquantitatively using transoesophageal echocardiography before discharge. RESULTS: We enrolled 399 patients (mean age 61±16 years; 58% women; 27% with a history of cardiac surgery). Mitral valve replacement was performed mainly for rheumatic disease (44%). Most patients were severely symptomatic (70% in New York Heart Association class III/IV). A mechanical prosthesis was implanted in 60% and a bioprosthesis in 40%. In-hospital mortality was 10%. Transoesophageal echocardiography was performed in 310 patients (77%); the main reasons for not performing transoesophageal echocardiography were frailty (n=40, 10%), early death (n=19, 5%) and contraindication for transoesophageal echocardiography (n=10, 3%). The overall rate of paravalvular regurgitation was 8% (n=25); a grade ≥2 was observed in five patients (2%), and two patients had to be reoperated on. Mitral annular calcification was the main factor associated with paravalvular regurgitation (P=0.01). CONCLUSIONS: Surgical mitral valve replacement was associated with significant in-hospital mortality and morbidity. Using systematic transoesophageal echocardiography assessment, paravalvular regurgitation was not uncommon (8%), and was significantly linked to mitral annulus calcification. However, clinically significant leakage (≥grade 2) was rare (2%).

Impact of Fetuin-A on progression of calcific aortic valve stenosis - The COFRASA - GENERAC study.

BACKGROUND: Aortic stenosis (AS) is an active disease, but the determinants of AS progression remain largely unknown. Low levels of Fetuin-A, a powerful inhibitor of ectopic calcification, have been linked to ectopic calcium tissue deposition but its role in AS progression has not been clearly evaluated. METHODS: In our ongoing prospective cohort (COFRASA/GENERAC), serum Fetuin-A level was measured at baseline and AS severity was evaluated at baseline and yearly thereafter using echocardiography (mean pressure gradient (MPG)) and computed tomography (degree of aortic valve calcification (AVC)). Annual progression was calculated as [(final measurement-baseline measurement)/follow-up duration] for both MPG and AVC measurements. RESULTS: We enrolled 296 patients (74 ±â€¯10 years,73% men); mean follow-up duration was 3.0 ±â€¯1.7 years. No correlation was found between baseline serum Fetuin-A (0.55 ±â€¯0.15 g/L) and baseline AS severity (r = 0.25, p = 0.87 for MPG; r = 0.06, p = 0.36 for AVC). More importantly, there was no correlation between baseline serum Fetuin-A level and AS progression either assessed using MPG or AVC (both r = 0.01, p = 0.82). In bivariate analysis, after adjustment for age, gender, baseline AS severity, or valve anatomy, Fetuin-A was not associated with AS progression (all p > 0.20). The absence of link with AS progression was further confirmed by the absence of link betwen serum Fetuin-A and the occurrence of AS-related events (p = 0.17). CONCLUSIONS: In a large prospective cohort of AS patients, serum Fetuin-A was not associated to hemodynamic or anatomic AS progression. Despite its capacity to inhibit ectopic calcium deposition, Fetuin-A serum level seemed to have minor influence on AS progression.

Timing of Referral of Patients With Severe Isolated Tricuspid Valve Regurgitation to Surgeons (from a French Nationwide Database).

Series evaluating the results of isolated tricuspid valve surgery (ITVS) are rare and often limited by small sample size, selection bias, and/or long period of enrollment. Based on a mandatory administrative national database, we collected all consecutive ITVS performed in France during a 2-year period (2013 and 2014), the type of intervention, clinical profile, and in-hospital mortality and complications. During the 2-year period, 241 patients underwent an ITVS in France (84 repairs and 157 replacements). In-hospital mortality was high (10%), and most patients experienced at least 1 complication (65%) with a 19% rate of major complications (death, need for dialysis, or need for mechanical support using extracorporeal membrane oxygenation). Consequently, hospital duration was remarkably long (26 ± 40 days). Congestive heart failure at presentation was associated with mortality and major complications rates (both p = 0.01). In conclusion, in a contemporary and consecutive series, ITVS was associated with a high mortality and morbidity predicted by clinical presentation at baseline. Our results suggest that patients are often referred too late and that an earlier intervention may improve immediate and possibly midterm outcomes. With the availability of transcatheter therapies in a near future, optimal timing of intervention in this population will be of utmost importance.

Ascending aorta dilatation rates in patients with tricuspid and bicuspid aortic stenosis: the COFRASA/GENERAC study.

Background: Ascending aorta (AA) dilatation is common in aortic valve stenosis (AS) but data regarding AA progression, its determinants and impact of valve anatomy [bicuspid (BAV), or tricuspid (TAV)] are scarce. Methods and Results: Asymptomatic AS patients enrolled in a prospective cohort (COFRASA/GENERAC) with at least 2 years of follow-up were considered in the present analysis. A transthoracic echocardiography (TTE) and a computed tomography (CT) scan were performed at inclusion and yearly thereafter. We enrolled 195 patients [mean gradient 22 ± 11 mmHg, 42 BAV patients (22%)]. Mean aorta diameters assessed using TTE were 35 ± 4 and 36 ± 5 mm at the sinuses of Valsalva and tubular level, respectively. Ascending aorta diameter was >40 mm in 29% of patients (24% in TAV vs. 52% in BAV, P < 0.01). Determinants of AA diameters were age, sex, BSA, and BAV, but not AS severity. After a mean follow-up of 3.8 ± 1.5years, AA enlargement rate assessed using TTE was +0.18 ± 0.34 mm/year and +0.36 ± 0.54 mm/year at the Valsalva and tubular level, respectively. Determinants of the progression of AA size were smaller AA diameter (P < 0.01) but not baseline AS severity or valve anatomy (all P > 0.05). Only four patients presented an AA progression ≥2 mm/year. Correlations between TTE and CT scan were excellent (all r >0.74) and similar results were obtained using CT. During follow-up, two BAV patients underwent a combined AA surgery; no surgery was primarily performed for AA aneurysm and no dissection was observed. Conclusion: In this prospective cohort of AS patients determinants of AA diameters were age, sex, BSA, and valve anatomy but not AS severity. AA progression rates were low and not influenced by AS severity or valve anatomy.

Prognostic Value of Exercise-Stress Echocardiography in Asymptomatic Patients With Aortic Valve Stenosis.

OBJECTIVES: This study sought to evaluate the prognostic value of mean pressure gradient (MPG) increase and peak systolic pulmonary artery pressure (SPAP) measured during exercise stress echocardiography in asymptomatic patients with aortic stenosis (AS). BACKGROUND: Exercise testing is recommended in asymptomatic AS patients, but the additional value of exercise-stress echocardiography, especially the prognostic value of MPG increase and peak SPAP, is still debated. METHODS: We enrolled all consecutive patients with pure, isolated, asymptomatic AS and preserved ejection fraction ≥50% and normal SPAP (<50 mm Hg) who underwent symptom-limited exercise echocardiography at our institution. Occurrence of AS-related events (symptoms or congestive heart failure) or occurrence of aortic valve replacement was recorded. RESULTS: We enrolled 148 patients (66 ± 15 years of age; 74% males; MPG: 47 ± 13 mm Hg; SPAP: 34 ± 6 mm Hg). No complications were observed. Thirty-six patients (24%) had an abnormal exercise test result (occurrence of symptoms, fall in blood pressure, and/or ST-segment depression) and were referred for surgery. Among the 112 patients with a normal exercise test result, 38 patients (34%) had abnormal exercise echocardiography scores (MPG increase >20 mm Hg and/or SPAP at peak exercise >60 mm Hg). These 112 patients were managed conservatively. During a mean follow-up of 14 ± 8 months, an AS-related event occurred in 30 patients, and 25 patients underwent surgery. Neither MPG increase >20 mm Hg nor peak SPAP >60 mm Hg was predictive of occurrence of AS-related events or aortic valve replacement (all p > 0.20). In contrast, baseline AS severity was an important prognostic factor (all p < 0.01). CONCLUSIONS: In this observational study including 148 patients with asymptomatic AS, we confirmed and extended the importance of exercise testing for unveiling functional limitation. More importantly, neither the increase in MPG nor in SPAP at peak exercise was predictive of outcome. Our results do not support the use of these parameters in risk-stratification and clinical management of asymptomatic AS patients.

Is tricuspid annuloplasty increasing surgical mortality and morbidity during mitral valve replacement? A single-centre experience.

BACKGROUND: Performance of tricuspid annuloplasty (TA) in patients undergoing mitral valve surgery is recommended based on the degree of tricuspid regurgitation and tricuspid annulus size, but is often underused. AIM: To evaluate the impact of combined TA on in-hospital outcome in patients undergoing mitral valve replacement (MVR). METHODS: We selected all consecutive patients who underwent MVR for native valve disease. Clinical, echocardiographic and in-hospital complications were obtained from chart review. RESULTS: We identified 287 patients (mean age 62±17 years; 44% men). Combined TA was performed in 165 patients (57%), who had more rheumatic disease (71% vs. 24%; P<0.0001) and mitral stenosis (55% vs. 22%; P<0.0001), but less endocarditis (4% vs. 31%; P<0.0001), were more often in atrial fibrillation (54% vs. 22%; P<0.0001), were more severely symptomatic (80% vs. 57%; P<0.0001), presented with a higher systolic pulmonary artery pressure (SPAP) (53±16 vs. 45±15mmHg; P=0.0002) and were less likely to have required emergency surgery (17% vs. 38%; P<0.0001). Despite this higher risk profile, in-hospital mortality was slightly lower (5% vs. 13%; P=0.02) and complication rates were similar (redo surgery 22% vs. 16% [P=0.18] and tamponade 20% vs. 15% [P=0.15]). After adjustment for age, sex, functional class, SPAP, emergency surgery and concomitant coronary artery bypass graft or aortic valve replacement surgery, combined TA was not associated with an increased rate of in-hospital death (P=0.08) or major complications (P=0.89). CONCLUSIONS: In a consecutive series of patients who underwent MVR, TA did not seem to have a negative impact on immediate outcome. Hence, additional performance of TA at the time of MVR should not be declined on the basis of an increased surgical risk.

Influence of metabolic syndrome and diabetes on progression of calcific aortic valve stenosis.

BACKGROUND: Determinants of the progression of aortic stenosis (AS) remained unclear. Metabolic syndrome (MetS) and diabetes are suspected to play an active role but literature is scarce and results conflicting. We sought to assess their impact in an ongoing prospective cohort of asymptomatic patients with at least mild AS. METHODS: We enrolled 203 patients (73±9years, 75% men) with at least 2years of follow-up. Risk-factors assessment was performed at baseline. Annual progression was calculated as [(final-baseline measurements)/follow-up duration] for both mean pressure gradient (MPG) and degree of aortic valve calcification (AVC) measurements. RESULTS: Ninety-nine patients (49%) had MetS and 50 (25%) had diabetes (including 39 with MetS). After a mean follow-up of 3.2±1.2years, AS progression was not different between patients with and without MetS either using MPG (+3±3 vs. +4±4mmHg/year, p=0.25) or AVC (+211±231 vs. +225±222AU/year, p=0.75). Same results were obtained for patients with diabetes (3±3 vs. 4±4mmHg/year p=0.53, 187±140 vs. 229±248AU/year p=0.99). MetS had no impact on AS progression in all tested subgroups based on age, statin prescription, valve anatomy and AS severity (all p≥0.10). CONCLUSION: In our prospective cohort of AS patients, we found no impact of MetS or diabetes on AS progression. Although MetS and diabetes should be actively treated, no impact on AS progression should be expected. Our results support the theory that if cardiovascular risk-factors may play a role at the early phase of AS disease they have no or limited influence on AS progression.

Anatomical features of acute mitral valve repair dysfunction: Additional value of three-dimensional echocardiography.

Recurrence of mitral regurgitation after mitral valve repair is correlated with unfavourable left ventricular remodelling and poor outcome. This pictorial review describes the echocardiographic features of three types of acute mitral valve repair dysfunction, and the additional value of three-dimensional echocardiography.

Determinants and prognostic value of B-type natriuretic peptide in patients with aortic valve stenosis.

BACKGROUND: The prognostic value of N-terminal fragment of pro B-type natriuretic peptide (Nt-proBNP) in aortic stenosis (AS) is still being debated. We sought to evaluate the determinants of Nt-proBNP in AS and its prognostic value in asymptomatic patients. METHODS: Patients with pure isolated at least mild degenerative AS enrolled in our prospective cohort (2006-2013) constituted our population. Clinical and biological measurements as well as echocardiographic evaluations were performed at study entry for all patients. Severe AS was defined by a valve area <1cm2. Asymptomatic patients were contacted every six months and seen every year. The occurrence of AS-related events (sudden death, congestive heart failure or new onset of symptoms) within two years was recorded prospectively. RESULTS: We enrolled 809 patients. Nt-proBNP increased with AS severity (p<0.0001) and symptomatic status (p<0.0001) but there was a wide overlap between groups of AS severity or symptomatic status. Nt-proBNP was the result of complex interactions between multiple determinants, including AS severity and symptomatic status but also age (p=0.0008), history of coronary artery disease (p=0.03), rhythm (p=0.007) and diastolic function (p<0.0001). Consequently, in asymptomatic patients with moderate/severe AS, normal ejection fraction and in sinus rhythm, Nt-proBNP was associated with AS-related events in univariate analysis (p=0.009) but not after adjustment for AS severity (p=0.12). Repeated Nt-proBNP measurements at one year did not improve their predictive value (p=0.43). CONCLUSION: This study highlights the limitations of Nt-proBNP in AS and raises caution regarding its use, at least as a single factor, in the decision-making process regarding asymptomatic patients with AS.