This study was conducted to define the association between serum B-type natriuretic peptide (BNP) activation and survival after the diagnosis of aortic stenosis (AS).
In AS, the link between BNP ...levels and clinical outcome is in dispute. Failure to account for the normal shifting of BNP ranges with aging in men and women, not using hard endpoints (survival), and not enrolling large series of patients have contributed to the uncertainty.
A program of prospective measurement of BNP levels with Doppler echocardiographic AS assessment during the same episode of care was conducted. BNP ratio (measured BNP/maximal normal BNP value specific to age and sex) >1 defined BNP clinical activation.
In 1,953 consecutive patients with at least moderate AS (aortic valve area 1.03 ± 0.26 cm(2); mean gradient 36 ± 19 mm Hg), median BNP level was 252 pg/ml (interquartile range: 98 to 592 pg/ml); BNP ratio 2.46 (interquartile range 1.03 to 5.66); ejection fraction (EF) 57% ± 15%, and symptoms present in 60% of patients. After adjustment for all survival determinants, BNP clinical activation (BNP ratio >1) independently predicted mortality after diagnosis (p < 0.0001; hazard ratio HR: 1.91; 95% CI: 1.55 to 2.35) and provided incremental power to the survival predictive model (p < 0.0001). Eight-year survival was 62 ± 3% with normal BNP levels, 44 ± 3% with BNP ratio of 1 to 2 (adjusted HR: 1.49; 95% CI: 1.17 to 1.90), 25 ± 4% with BNP ratio of 2 to 3 (adjusted HR: 2.12; 95% CI: 1.63 to 2.75), and 15 ± 2% with BNP ratio of ≥3 (adjusted HR: 2.43; 95% CI: 1.94 to 3.05). This strong link to survival was confirmed in asymptomatic patients with normal EF (adjusted HR: 2.35 95% CI: 1.57 to 3.56 for BNP clinical activation and 2.10 95% CI: 1.32 to 3.36 for BNP ratio of 1 to 2, 2.25 95% CI: 1.31 to 3.87 for BNP ratio of 2 to 3, 3.93 95% CI: 2.40 to 6.43 for BNP ratio of ≥3). Aortic valve replacement was associated with survival improved by a similarly high margin (p = 0.54) with BNP ratio of <2 (HR: 0.68; 95% CI: 0.52 to 0.89; p = 0.003) or BNP ratio of >2 (HR: 0.56; 95% CI: 0.47 to 0.66; p < 0.0001).
In this large series of patients with AS, BNP clinical activation was associated with excess long-term mortality incrementally and independently of all baseline characteristics. Higher mortality with higher BNP clinical activation, even in asymptomatic patients, emphasizes the importance of appropriate clinical interpretation of BNP levels in managing patients with AS.
Abstract Objective The timing of surgical correction of mitral regurgitation remains controversial. A major source of dispute regards the potential short- and long-term postoperative outcome penalty ...associated with the type of guideline-based indication for surgery. Methods Between 1990 and 2000, 1512 patients (aged 64 ± 14 years, mitral prolapse in 89%, valve repair in 88%) underwent surgical correction of pure organic mitral regurgitation. Patients were stratified according to surgical indication into class I triggers (ClassI-T: heart failure symptoms, ejection fraction <60%, end-systolic diameter ≥40 mm, n = 794), class II triggers based on clinical complications (ClassII-CompT: atrial fibrillation or pulmonary hypertension, n = 195), or early class II triggers based on a combination of severe mitral regurgitation and high probability of valve repair (ClassII-EarlyT: n = 523). Results Operative mortality was highest with ClassI-T (1.1% vs 0% and 0%, P = .016). Long-term survival was lower with ClassI-T (15-year 42% ± 2%; adjusted hazard ratio HR, 1.89; 95% confidence interval CI, 1.53-2.34; P < .0001) and ClassII-CompT (15-year 53% ± 4%, adjusted HR, 1.39; 95% CI, 1.04-1.84; P = .027) versus ClassII-EarlyT (15-year 70% ± 3%, P < .0001). Postoperative excess mortality with ClassI-T and ClassII-CompT was confirmed by age stratification, inverse probability weighting, and expected survival adjustment. Excess postoperative heart failure was high with ClassI-T (adjusted HR, 2.49; 95% CI, 1.82-3.47; P < .0001) and ClassII-CompT (adjusted HR, 1.98; 95% CI, 1.30-3.00; P = .002). Conclusions The type of guideline-based indication for surgical correction of organic mitral regurgitation is associated with profound outcome consequences on long-term postoperative mortality and heart failure, despite low operative risk and high repair rates. Conversely, surgical correction of severe mitral regurgitation based on high probability of repair (ClassII-EarlyT) is associated with improved survival and low heart failure risk and should be the preferred strategy in valve centers offering low operative risk and high repair rates.
CT aortic valve calcium score (AVC
) and density (AVC
) thresholds have been recommended for aortic stenosis (AS) severity assessment in tricuspid aortic valve (TAV). We aimed to compare AVC
and AVC
...in bicuspid aortic valve (BAV) versus TAV.
Retrospective single-centre study of patients with echocardiographic AS-severity and CT-AVC assessments within 6 months, and left ventricular ejection fraction ≥50%, all referred for clinical AS evaluation.Severe AS was defined as aortic valve area (AVA) ≤1 cm
or indexed AVA ≤0.6cm
/m
plus mean gradient ≥40 mm Hg or peak velocity ≥4 m/s. AVC was assessed by Agatston method.
Of the 1957 patients, 328 had BAV and 1629 had TAV, age 65±11 vs 80±9 years (p<0.001), men 65% vs 56% (p=0.006), respectively. BAV morphology was associated with higher AVC
and AVC
independent of age, comorbidities and AS severity (p<0.001) in men only (sex and BAV interaction p<0.001). In patients with severe AS, mean AVC
and AVC
were higher in BAV-men than that in TAV-men (both p<0.001), but similar in BAV-women and TAV-women (both p≥0.4). Such patterns remained the same after adjustment for clinical covariates and AS severity. Best thresholds for severe AS diagnosis in BAV-men were 2916 AU by AVC
and 600 AU/cm
by AVC
which were higher than the guideline-recommended thresholds, while thresholds in BAV-women (1036 AU and 282 AU/cm
) were similar to guideline-recommended ones.
Valve calcification in AS differs according to valve morphology and sex. BAV-men with severe AS exhibit greater AVC
and AVC
than TAV-men. This presents a diagnostic challenge to the current guidelines, which needs confirmation in larger studies.
The effective orifice area (EOA) estimated by transthoracic Doppler echocardiography (TTE) via the continuity equation is commonly used to determine the severity of aortic stenosis (AS). However, ...there are often discrepancies between TTE-derived EOA and invasive indices of stenosis, thus raising uncertainty about actual definite severity. Cardiovascular magnetic resonance (CMR) has emerged as an alternative method for non-invasive estimation of valve EOA. The objective of this study was to assess the concordance between TTE and CMR for the estimation of valve EOA.
31 patients with mild to severe AS (EOA range: 0.72 to 1.73 cm2) and seven (7) healthy control subjects with normal transvalvular flow rate underwent TTE and velocity-encoded CMR. Valve EOA was calculated by the continuity equation. CMR revealed that the left ventricular outflow tract (LVOT) cross-section is typically oval and not circular. As a consequence, TTE underestimated the LVOT cross-sectional area (ALVOT, 3.84 ± 0.80 cm2) compared to CMR (4.78 ± 1.05 cm2). On the other hand, TTE overestimated the LVOT velocity-time integral (VTILVOT: 21 ± 4 vs. 15 ± 4 cm). Good concordance was observed between TTE and CMR for estimation of aortic jet VTI (61 ± 22 vs. 57 ± 20 cm). Overall, there was a good correlation and concordance between TTE-derived and CMR-derived EOAs (1.53 ± 0.67 vs. 1.59 ± 0.73 cm2, r = 0.92, bias = 0.06 ± 0.29 cm2). The intra- and inter- observer variability of TTE-derived EOA was 5 ± 5% and 9 ± 5%, respectively, compared to 2 ± 1% and 7 ± 5% for CMR-derived EOA.
Underestimation of ALVOT by TTE is compensated by overestimation of VTILVOT, thereby resulting in a good concordance between TTE and CMR for estimation of aortic valve EOA. CMR was associated with less intra- and inter- observer measurement variability compared to TTE. CMR provides a non-invasive and reliable alternative to Doppler-echocardiography for the quantification of AS severity.
Myocardial fibrosis is a key mechanism of left ventricular decompensation in aortic stenosis and can be quantified using cardiovascular magnetic resonance (CMR) measures such as extracellular volume ...fraction (ECV%). Outcomes following aortic valve intervention may be linked to the presence and extent of myocardial fibrosis.
This study sought to determine associations between ECV% and markers of left ventricular decompensation and post-intervention clinical outcomes.
Patients with severe aortic stenosis underwent CMR, including ECV% quantification using modified Look-Locker inversion recovery–based T1 mapping and late gadolinium enhancement before aortic valve intervention. A central core laboratory quantified CMR parameters.
Four-hundred forty patients (age 70 ± 10 years, 59% male) from 10 international centers underwent CMR a median of 15 days (IQR: 4 to 58 days) before aortic valve intervention. ECV% did not vary by scanner manufacturer, magnetic field strength, or T1 mapping sequence (all p > 0.20). ECV% correlated with markers of left ventricular decompensation including left ventricular mass, left atrial volume, New York Heart Association functional class III/IV, late gadolinium enhancement, and lower left ventricular ejection fraction (p < 0.05 for all), the latter 2 associations being independent of all other clinical variables (p = 0.035 and p < 0.001). After a median of 3.8 years (IQR: 2.8 to 4.6 years) of follow-up, 52 patients had died, 14 from adjudicated cardiovascular causes. A progressive increase in all-cause mortality was seen across tertiles of ECV% (17.3, 31.6, and 52.7 deaths per 1,000 patient-years; log-rank test; p = 0.009). Not only was ECV% associated with cardiovascular mortality (p = 0.003), but it was also independently associated with all-cause mortality following adjustment for age, sex, ejection fraction, and late gadolinium enhancement (hazard ratio per percent increase in ECV%: 1.10; 95% confidence interval 1.02 to 1.19; p = 0.013).
In patients with severe aortic stenosis scheduled for aortic valve intervention, an increased ECV% is a measure of left ventricular decompensation and a powerful independent predictor of mortality.
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Computed tomography aortic valve calcium scoring (CT-AVC) holds promise for the assessment of patients with aortic stenosis (AS). We sought to establish the clinical utility of CT-AVC in an ...international multicenter cohort of patients.
Patients with AS who underwent ECG-gated CT-AVC within 3 months of echocardiography were entered into an international, multicenter, observational registry. Optimal CT-AVC thresholds for diagnosing severe AS were determined in patients with concordant echocardiographic assessments, before being used to arbitrate disease severity in those with discordant measurements. In patients with long-term follow-up, we assessed whether CT-AVC thresholds predicted aortic valve replacement and death. In 918 patients from 8 centers (age, 77±10 years; 60% men; peak velocity, 3.88±0.90 m/s), 708 (77%) patients had concordant echocardiographic assessments, in whom CT-AVC provided excellent discrimination for severe AS (C statistic: women 0.92, men 0.89). Our optimal sex-specific CT-AVC thresholds (women 1377 Agatston unit and men 2062 Agatston unit) were nearly identical to those previously reported (women 1274 Agatston unit and men 2065 Agatston unit). Clinical outcomes were available in 215 patients (follow-up 1029 126-2251 days). Sex-specific CT-AVC thresholds independently predicted aortic valve replacement and death (hazard ratio, 3.90 95% confidence interval, 2.19-6.78;
<0.001) after adjustment for age, sex, peak velocity, and aortic valve area. Among 210 (23%) patients with discordant echocardiographic assessments, there was considerable heterogeneity in CT-AVC scores, which again were an independent predictor of clinical outcomes (hazard ratio, 3.67 95% confidence interval, 1.39-9.73;
=0.010).
Sex-specific CT-AVC thresholds accurately identify severe AS and provide powerful prognostic information. These findings support their integration into routine clinical practice.
URL: http://www.clinicaltrials.gov. Unique identifiers: NCT01358513, NCT02132026, NCT00338676, NCT00647088, NCT01679431.
N-terminal pro–B-type natriuretic peptide (NT-proBNP) may reflect early prognosis in patients with valvular heart disease (VHD).
The aim of this study was to examine the association between NT-proBNP ...and mortality in elderly patients with VHD.
A total of 5,983 elderly patients (age ≥60 years) with moderate or severe VHD underwent echocardiography and NT-proBNP measurement. VHD examined included aortic stenosis, aortic regurgitation, mitral stenosis, mitral regurgitation, tricuspid regurgitation, and multivalvular heart disease. NT-proBNP ratio was defined as measured NT-proBNP relative to the maximal normal values specific to age and sex. Disease-specific thresholds were defined on the basis of penalized splines and maximally selected rank statistics.
The cohort had a mean age of 71.1 ± 7.6 years. At 1-year follow-up, 561 deaths (9.4%) had occurred. In penalized splines, relative hazards showed a monotonic increase with greater NT-proBNP ratio for death with different VHDs (p < 0.001 for all) except mitral stenosis. Higher NT-proBNP ratio, categorized by disease-specific thresholds, was independently associated with mortality (overall adjusted hazard ratio: 1.99; 95% confidence interval: 1.76 to 2.24; p < 0.001). Different subtypes of VHD all incurred excess mortality with elevated NT-proBNP ratio, with the strongest association detected for aortic stenosis (adjusted hazard ratio: 10.5; 95% confidence interval: 3.9 to 28.27; p < 0.001). The addition of NT-proBNP ratio to the prediction algorithm including traditional risk factors improved outcome prediction (overall net reclassification index = 0.28; 95% CI: 0.24 to 0.34; p < 0.001; likelihood ratio test p < 0.001). Results remained consistent in patients under medical care, with normal left ventricular ejection fractions, and with primary VHD.
NT-proBNP provides incremental prognostic information for mortality in various VHDs. It could aid in risk stratification as a pragmatic and versatile biomarker in elderly patients.
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