Increased hsCRP is associated with higher risk of aortic valve replacement in patients with aortic stenosis.

Objective To investigate relations between inflammation and aortic valve stenosis (AS) by measuring high-sensitivity C-reactive protein, at baseline (hsCRP0) and after 1 year (hsCRP1) and exploring associations with aortic valve replacement (AVR). Design We examined 1423 patients from the Simvastatin and Ezetimibe in Aortic Stenosis study. Results During first year of treatment, hsCRP was reduced both in patients later receiving AVR (2.3 [0.9-4.9] to 1.8 [0.8-5.4] mg/l, p < 0.001) and not receiving AVR (1.90 [0.90-4.10] to 1.3 [0.6-2.9] mg/l, p < 0.001). In Cox-regression analyses, hsCRP1 predicted later AVR (HR = 1.17, p < 0.001) independently of hsCRP0 (HR = 0.96, p = 0.33), aortic valve area (AVA) and other risk factors. A higher rate of AVR was observed in the group with high hsCRP0 and an increase during the first year (AVRhighCRP0CRP1inc = 47.3% versus AVRhighCRP0CRP1dec = 27.5%, p < 0.01). The prognostic benefit of a 1-year reduction in hsCRP was larger in patients with high versus low hsCRP0 eliminating the difference in incidence of AVR between high versus low hsCRP0 (AVRhighCRP0CRP1dec = 27.5% versus AVRlowCRP0CRP1dec = 25.8%, p = 0.66) in patients with reduced hsCRP during the first year. Conclusions High hsCRP1 or an increase in hsCRP during the first year of follow-up predicted later AVR independently of AVA, age, gender and other risk factors, although no significant improvement in C-statistics was observed.

ESC Working Group on Valvular Heart Disease Position Paper: assessing the risk of interventions in patients with valvular heart disease.

AIMS: Risk scores provide an important contribution to clinical decision-making, but their validity has been questioned in patients with valvular heart disease (VHD), since current scores have been mainly derived and validated in adults undergoing coronary bypass surgery. The Working Group on Valvular Heart Disease of the European Society of Cardiology reviewed the performance of currently available scores when applied to VHD, in order to guide clinical practice and future development of new scores. METHODS AND RESULTS: The most widely used risk scores (EuroSCORE, STS, and Ambler score) were reviewed, analysing variables included and their predictive ability when applied to patients with VHD. These scores provide relatively good discrimination, i.e. a gross estimation of risk category, but cannot be used to estimate the exact operative mortality in an individual patient because of unsatisfactory calibration. CONCLUSION: Current risk scores do not provide a reliable estimate of exact operative mortality in an individual patient with VHD. They should therefore be interpreted with caution and only used as part of an integrated approach, which incorporates other patient characteristics, the clinical context, and local outcome data. Future risk scores should include additional variables, such as cognitive and functional capacity and be prospectively validated in high-risk patients. Specific risk models should also be developed for newer interventions, such as transcatheter aortic valve implantation.

Outcome of patients with low-gradient "severe" aortic stenosis and preserved ejection fraction.

BACKGROUND: Retrospective studies have suggested that patients with a low transvalvular gradient in the presence of an aortic valve area < 1.0 cm² and normal ejection fraction may represent a subgroup with an advanced stage of aortic valve disease, reduced stroke volume, and poor prognosis requiring early surgery. We therefore evaluated the outcome of patients with low-gradient "severe" stenosis (defined as aortic valve area < 1.0 cm² and mean gradient ≤ 40 mm Hg) in the prospective Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study. METHODS AND RESULTS: Outcome in patients with low-gradient "severe" aortic stenosis was compared with outcome in patients with moderate stenosis (aortic valve area 1.0 to 1.5 cm²; mean gradient 25 to 40 mm Hg). The primary end point of aortic valve events included death from cardiovascular causes, aortic valve replacement, and heart failure due to aortic stenosis. Secondary end points were major cardiovascular events and cardiovascular death. In 1525 asymptomatic patients (mean age, 67 ± 10 years; ejection fraction, ≥ 55%), baseline echocardiography revealed low-gradient severe stenosis in 435 patients (29%) and moderate stenosis in 184 (12%). Left ventricular mass was lower in patients with low-gradient severe stenosis than in those with moderate stenosis (182 ± 64 versus 212 ± 68 g; P < 0.01). During 46 months of follow-up, aortic valve events occurred in 48.5% versus 44.6%, respectively (P = 0.37; major cardiovascular events, 50.9% versus 48.5%, P = 0.58; cardiovascular death, 7.8% versus 4.9%, P = 0.19). Low-gradient severe stenosis patients with reduced stroke volume index (≤ 35 mL/m²; n = 223) had aortic valve events comparable to those in patients with normal stroke volume index (46.2% versus 50.9%; P = 0.53). CONCLUSIONS: Patients with low-gradient "severe" aortic stenosis and normal ejection fraction have an outcome similar to that in patients with moderate stenosis.

Global left ventricular load in asymptomatic aortic stenosis: covariates and prognostic implication (the SEAS trial).

INTRODUCTION: Valvuloarterial impedance (Zva) is a measure of global (combined valvular and arterial) load opposing left ventricular (LV) ejection in aortic stenosis (AS). The present study identified covariates and tested the prognostic significance of global LV load in patients with asymptomatic AS. METHODS: 1418 patients with mild-moderate, asymptomatic AS in the Simvastatin Ezetimibe in Aortic Stenosis (SEAS) study were followed for a mean of 43±14 months during randomized, placebo-controlled treatment with combined simvastatin 40 mg and ezetimibe 10 mg daily. High global LV load was defined as Zva >5 mm Hg/ml/m2. The impact of baseline global LV load on rate of major cardiovascular (CV) events, aortic valve events and total mortality was assessed in Cox regression models reporting hazard ratio (HR) and 95% Confidence Intervals (CI). RESULTS: High global LV load was found in 18% (n=252) of patients and associated with female gender, higher age, hypertension, more severe AS and lower ejection fraction (all p<0.05). A total of 476 major CV events, 444 aortic valve events and 132 deaths occurred during follow-up. In multivariate Cox regression analyses, high global LV load predicted higher rate of major CV events (HR 1.35 [95% CI 1.08-1.71], P=0.010) and aortic valve events (HR 1.41 [95% CI 1.12-1.79], P=0.004) independent of hypertension, LV ejection fraction, female gender, age, abnormal LV geometry and AS severity, but failed to predict mortality. CONCLUSION: In asymptomatic AS, assessment of global LV load adds complementary information on prognosis to that provided by hypertension or established prognosticators like AS severity and LV ejection fraction.

Intensive lipid lowering with simvastatin and ezetimibe in aortic stenosis.

BACKGROUND: Hyperlipidemia has been suggested as a risk factor for stenosis of the aortic valve, but lipid-lowering studies have had conflicting results. METHODS: We conducted a randomized, double-blind trial involving 1873 patients with mild-to-moderate, asymptomatic aortic stenosis. The patients received either 40 mg of simvastatin plus 10 mg of ezetimibe or placebo daily. The primary outcome was a composite of major cardiovascular events, including death from cardiovascular causes, aortic-valve replacement, nonfatal myocardial infarction, hospitalization for unstable angina pectoris, heart failure, coronary-artery bypass grafting, percutaneous coronary intervention, and nonhemorrhagic stroke. Secondary outcomes were events related to aortic-valve stenosis and ischemic cardiovascular events. RESULTS: During a median follow-up of 52.2 months, the primary outcome occurred in 333 patients (35.3%) in the simvastatin-ezetimibe group and in 355 patients (38.2%) in the placebo group (hazard ratio in the simvastatin-ezetimibe group, 0.96; 95% confidence interval [CI], 0.83 to 1.12; P=0.59). Aortic-valve replacement was performed in 267 patients (28.3%) in the simvastatin-ezetimibe group and in 278 patients (29.9%) in the placebo group (hazard ratio, 1.00; 95% CI, 0.84 to 1.18; P=0.97). Fewer patients had ischemic cardiovascular events in the simvastatin-ezetimibe group (148 patients) than in the placebo group (187 patients) (hazard ratio, 0.78; 95% CI, 0.63 to 0.97; P=0.02), mainly because of the smaller number of patients who underwent coronary-artery bypass grafting. Cancer occurred more frequently in the simvastatin-ezetimibe group (105 vs. 70, P=0.01). CONCLUSIONS: Simvastatin and ezetimibe did not reduce the composite outcome of combined aortic-valve events and ischemic events in patients with aortic stenosis. Such therapy reduced the incidence of ischemic cardiovascular events but not events related to aortic-valve stenosis. (ClinicalTrials.gov number, NCT00092677.)

Actual management of patients with asymptomatic aortic valve disease: how practice fits with guidelines.

BACKGROUND: Intervention is advised in selected asymptomatic patients with aortic valve disease. However, little is known regarding their actual management. METHODS: The Euro Heart Survey was designed to evaluate practices. Severe isolated aortic stenosis (AS) was defined by a valve area < or = 0.6 cm2/m2 body surface area or mean gradient > or = 50 mm Hg. Severe aortic regurgitation (AR) was defined by a grade > or = 3/4. Patients were classified as asymptomatic when they were in New York Heart Association class I and were without angina. Decision to operate was analyzed by comparing patient characteristics with the American College of Cardiology/American Heart Association recommendations. RESULTS: Of the 5001 patients, 136 had severe, isolated, and asymptomatic aortic valve disease (84 with AS and 52 with AR). Stress testing was performed in only 6 patients (4%). A decision to operate was taken in 45 patients (54%) with AS and 21 (40%) with AR. Indications for surgery were in accordance with the American College of Cardiology/American Heart Association guidelines in 57 patients (68%) with AS and in 41 (83%) with AR. However, the decision to operate was frequently based on class IIb recommendations in patients with AS. Intervention was "overused" in 18 patients with AS (21%) and in 5 (9%) with AR. Intervention was "underused" in 9 patients (11%) with AS and in 4 (8%) with AR. CONCLUSIONS: In asymptomatic patients with severe aortic valve disease, a decision to operate is frequently taken; and it is most often in agreement with guidelines, although often based on low-level recommendations.

Design and baseline characteristics of the simvastatin and ezetimibe in aortic stenosis (SEAS) study.

Aortic valve stenosis and atherosclerotic disease have several risk factors in common, in particular, hypercholesterolemia. Histologically, the diseased valves appear to have areas of inflammation much like atherosclerotic plaques. The effect of lipid-lowering therapy on the progression of aortic stenosis (AS) is unclear, and there are no randomized treatment trials evaluating cardiovascular morbidity and mortality in such patients. The Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) Study is a randomized, double-blind, placebo-controlled, multicenter study of a minimum 4 years' duration investigating the effect of lipid lowering with ezetimibe/simvastatin 10/40 mg/day in patients with asymptomatic AS with peak transvalvular jet velocity 2.5 to 4.0 m/s. Primary efficacy variables include aortic valve surgery and ischemic vascular events, including cardiovascular mortality, and second, the effect on echocardiographically evaluated progression of AS. The SEAS Study randomly assigned 1,873 patients (age 68+/-10 years, 39% women, mean transaortic maximum velocity 3.1+/-0.5 m/s) from 173 sites. Other baseline characteristics were mean blood pressure of 145+/-20/82+/-10 mm Hg (51% hypertensive); 55% were current or previous smokers; and most were overweight (mean body mass index 26.9 kg/m2). At baseline, mean total cholesterol was 5.7+/-1.0 mmol/L (222 mg/dl), low-density lipoprotein cholesterol was 3.6+/-0.9 mmol/L (139 mg/dl), high-density lipoprotein cholesterol was 1.5+/-0.4 mmol/L (58 mg/dl), and triglycerides were 1.4+/-0.7 mmol/L (126 mg/dl). The SEAS Study is the largest randomized trial to date in patients with AS and will allow determination of the prognostic value of aggressive lipid lowering in such patients.

Valvular heart disease in the community: a European experience.

The Euro Heart Survey on valvular heart disease included 5001 patients from 92 centers in 25 European countries in 2001: 71.9% had native valve disease and 28.1% had previously undergone valve surgery. Aortic stenosis (AS) and mitral regurgitation (MR) accounted for 43.1 and 33.6%, respectively, of single-valve diseases and were mostly caused by degenerative diseases. Mean age was 69 and 65 years, respectively, and at least one comorbidity was present in 36.3% of patients with AS and 41.7% with MR. Analysis of the therapeutic decision in patients with severe valve diseases showed that symptomatic patients were frequently denied surgery (32.3% in AS after the age of 75 and 51.3% in MR), more on the basis of age and left ventricular function than comorbidities. There was a better concordance between practice and guidelines concerning interventions in asymptomatic patients. These findings underline the need for better implementation of guidelines.

Comparison of Frequency of Ischemic Cardiovascular Events in Patients With Aortic Stenosis With Versus Without Asymmetric Septal Hypertrophy (from the SEAS Trial).

Asymmetric interventricular septum hypertrophy (ASH) has been associated with increased perioperative morbidity and mortality in patients with severe, symptomatic aortic valve stenosis (AS). Less is known about the prognostic impact of ASH during progression of AS. Clinical, echocardiographic, and outcome data from 1,691 patients with initially asymptomatic, mostly moderate AS, participating in the Simvastatin Ezetimibe in Aortic Stenosis (SEAS) study was used. ASH was considered present if interventricular septum/posterior wall thickness ratio in end-diastole ≥1.5. The associations of ASH with hazard rate of ischemic cardiovascular events were tested in time-dependent Cox regression analyses. Based on the presence of ASH at study echocardiograms, the study population was grouped in to a no-ASH, nonpersistent ASH, persistent ASH, and new-onset ASH groups. During a median of 4.3 years of follow-up, ASH persisted or developed in 17% of patients. Persistent or new-onset ASH was characterized by higher left ventricular mass index and ejection fraction at baseline (both p <0.05) but not with female gender or hypertension. In time-varying Cox regression analyses adjusting for these confounders, persistent or new-onset ASH was associated with higher hazard rate of ischemic cardiovascular events (hazard rate 1.45; 95% confidence interval 1.09 to 1.91, p = 0.01), in particular coronary artery bypass grafting (hazard rate 1.69; 95% confidence interval 1.17 to 2.47; p = 0.006), whereas no association with increased mortality was found. In conclusion, in patients with AS without diabetes or known renal or cardiovascular disease participating in the SEAS study, persistent or new-onset ASH during progression of AS was associated with higher rate of ischemic cardiovascular events.

Impact of stroke volume on cardiovascular risk during progression of aortic valve stenosis.

OBJECTIVE: In severe aortic valve stenosis (AS), low left ventricular (LV) stroke volume has been associated with increased cardiovascular (CV) mortality, but this association has not been explored during progression of AS in a large prospective study. METHODS: In 1671 patients from the Simvastatin Ezetimibe in Aortic Stenosis (SEAS) study, the association of stroke volume indexed for body surface area (SVI) with major CV events during a median of 4.3-year follow-up was assessed in Cox and time-varying Cox regression analyses. Low SVI was defined as <35 mL/m2. RESULTS: Peak aortic jet velocity in the total study population was 3.1 ±0.7 m/s. Low SVI was found in 23% at baseline and associated with higher age, body mass index (BMI), heart rate and global LV load, and with lower mean aortic gradient, aortic valve area index, energy loss index, LV mass and ejection fraction and more often inconsistent AS grading (all p<0.05). A 5 mL/m2 lower SVI at baseline was associated with higher HRs of major CV events (n=544) (HR 1.09, 95% CI 1.05 to 1.13, p<0.001) and higher total mortality (n=147) (HR 1.08, 95% CI 1.01 to 1.16, p=0.038), independent of age, sex, atrial fibrillation, mean aortic gradient, LV ejection fraction, LV mass, BMI and study treatment. Adjusting for the same covariates, low SVI at baseline and in-study low SVI were also associated with increased rate of major CV events. CONCLUSION: In patients with AS in the SEAS study, lower baseline SVI was associated with higher HR of major CV events and total mortality independent of major confounders. TRIAL REGISTRATION NUMBER: NCT00092677: Results.

SuPAR Predicts Cardiovascular Events and Mortality in Patients With Asymptomatic Aortic Stenosis.

BACKGROUND: Soluble urokinase plasminogen activator receptor (suPAR) is an inflammatory marker associated with subclinical cardiovascular damage and cardiovascular events. Whether suPAR is of prognostic value in asymptomatic patients with aortic stenosis (AS) remains unknown. METHODS: Plasma suPAR levels were measured in 1503 patients with a mean age of 68 years who were recruited in the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study. Cox regression analysis was performed to evaluate associations between suPAR and the composite end points of ischemic cardiovascular events (ICEs), aortic valve events (AVEs), cardiovascular and all-cause mortality after adjusting for traditional cardiovascular risk factors, and allocation to treatment. RESULTS: The multivariate adjusted hazard ratio (HR) (95% confidence interval [CI]) per unit log2 ng/mL increase in suPAR was HR, 1.5; 95% CI, 1.2-1.9; P = 0.002 for ICEs; HR, 1.2; 95% CI, 0.9-1.5; P = 0.071) for AVEs; HR, 2.0; 95% CI, 1.2-3.3; P = 0.007) for cardiovascular mortality, and HR, 2.0; 95% CI, 1.4-2.9; P < 0.001 for all-cause mortality. CONCLUSIONS: In patients with mild-moderate AS, suPAR is independently associated with the incidence of ICEs, cardiovascular mortality, and all-cause mortality.

Sex differences in cardiovascular outcome during progression of aortic valve stenosis.

OBJECTIVE: Women with severe aortic valve stenosis (AS) have better LV systolic function and more concentric LV geometry than their male counterparts. However, sex differences in cardiovascular (CV) outcome during progression of AS have not been reported from a longitudinal prospective study. METHODS: Doppler echocardiography and CV events were recorded during a median of 4.0 years in 979 men and 632 women aged 28-86 (mean 67±10) years in the Simvastatin Ezetimibe in Aortic Stenosis (SEAS) study. LV systolic function was assessed by EF and midwall shortening (MWS). Study outcomes were AS-related events, ischaemic CV events and total mortality. RESULTS: The annular cumulative incidence of AS events, ischaemic CV events and death was 8.1%, 3.4% and 2.8% in women, and 8.9%, 4.4% and 2.4% in men, respectively. Women and men had similar AS progression rate whether measured by peak jet velocity, mean gradient or valve area. In multivariate analyses, female sex independently predicted less reduction in LV MWS and EF during follow-up (both p<0.05). In time-varying Cox analyses, women had a 40% lower rate of ischaemic CV events (95% CI 21% to 54%), in particular, more than 50% lower rate of stroke and coronary artery bypass grafting, and a 31% lower all-cause mortality (95% CI 1% to 51%), independent of active study treatment, age and hypertension, as well as time-varying valve area, low systolic function and abnormal LV geometry. AS event rate did not differ by sex. CONCLUSIONS: In the SEAS study, women and men had similar rates of AS progression and AS-related events. However, women had lower total mortality and ischaemic CV event rate than men independent of confounders. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov identifier: NCT00092677.

Effect of Randomized Lipid Lowering With Simvastatin and Ezetimibe on Cataract Development (from the Simvastatin and Ezetimibe in Aortic Stenosis Study).

Recent American College of Cardiology/American Heart Association guidelines on statin initiation on the basis of total atherosclerotic cardiovascular disease risk argue that the preventive effect of statins on cardiovascular events outweigh the side effects, although this is controversial. Studies indicate a possible effect of statin therapy on reducing risk of lens opacities. However, the results are conflicting. The Simvastatin and Ezetimibe in Aortic Stenosis study (NCT00092677) enrolled 1,873 patients with asymptomatic aortic stenosis and no history of diabetes, coronary heart disease, or other serious co-morbidities were randomized (1:1) to double-blind 40 mg simvastatin plus 10 mg ezetimibe versus placebo. The primary end point in this substudy was incident cataract. Univariate and multivariate Cox models were used to analyze: (1) if the active treatment reduced the risk of the primary end point and (2) if time-varying low-density lipoproteins (LDL) cholesterol lowering (annually assessed) was associated with less incident cataract per se. During an average follow-up of 4.3 years, 65 patients (3.5%) developed cataract. Mean age at baseline was 68 years and 39% were women. In Cox multivariate analysis adjusted for age, gender, prednisolone treatment, smoking, baseline LDL cholesterol and high sensitivity C-reactive protein; simvastatin plus ezetimibe versus placebo was associated with 44% lower risk of cataract development (hazard ratio 0.56, 95% confidence interval 0.33 to 0.96, p = 0.034). In a parallel analysis substituting time-varying LDL-cholesterol with randomized treatment, lower intreatment LDL-cholesterol was in itself associated with lower risk of incident cataract (hazard ratio 0.78 per 1 mmol/ml lower total cholesterol, 95% confidence interval 0.64 to 0.93, p = 0.008). In conclusion, randomized treatment with simvastatin plus ezetimibe was associated with a 44% lower risk of incident cataract development. This effect should perhaps be considered in the risk-benefit ratio of statin treatment.

Standards for heart valve surgery in a 'Heart Valve Centre of Excellence'.

Surgical centres of excellence should include multidisciplinary teams with specialist expertise in imaging, clinical assessment and surgery for patients with heart valve disease. There should be structured training programmes for the staff involved in the periprocedural care of the patient and these should be overseen by national or international professional societies. Good results are usually associated with high individual and centre volumes, but this relationship is complex. Results of surgery should be published by centre and should include rates of residual regurgitation for mitral repairs and reoperation rates matched to the preoperative pathology and risk.

High sensitivity C reactive protein as a prognostic marker in patients with mild to moderate aortic valve stenosis during lipid-lowering treatment: an SEAS substudy.

AIMS: To assess the prognostic importance of high-sensitive C reactive protein (hsCRP) in patients with mild to moderate aortic valve stenosis during placebo or simvastatin/ezetimibe treatment in Simvastatin and Ezetimibe in Aortic Stenosis (SEAS). METHODS AND RESULTS: In 1620 SEAS patients, we measured lipids and hsCRP at baseline and after 1 year of treatment and registered during 4 years of follow-up major cardiovascular events (MCE) composed of ischaemic cardiovascular events (ICE) and aortic valve-related events (AVE). Simvastatin/ezetimibe reduced low-density lipoprotein cholesterol (3.49 (2.94 to 4.15) to 1.32 (1.02 to 1.69) vs 3.46 (2.92 to 4.08) to 3.34 (2.81 to 3.92) mmol/L) and hsCRP (2.1 (0.9 to 4.1) to 1.2 (0.6 to 2.4) vs 2.2 (0.9 to 4.9) to 1.8 (0.85 to 4.35) mg/L, all p<0.05) during the first year of treatment. In multivariable Cox regression analysis adjusting for traditional risk factors and baseline hsCRP, ICE was associated with a 1-year increase of hsCRP (HR=1.19 (95% CI 1.12 to 1.25), p<0.001) but not with active treatment (HRTreatment=0.86 (0.67 to 1.13), p=0.28). Patients in the top quartile of baseline hsCRP versus the rest were associated with a higher risk of MCE (HR=1.34(1.09 to 1.64), p=0.02). The prognostic benefit of reduction in hsCRP after 1 year was significantly larger (p<0.01 for interaction) in patients with high versus low baseline hsCRP; hence, a reduction in hsCRP abolished the difference in incidence of MCE between high versus low baseline hsCRP in patients with reduced hsCRP (31.1 vs 31.9%, NS) in contrast to patients with increased hsCRP. CONCLUSIONS: The treatment-associated reduction in ICE was in part related to a reduction in hsCRP but not in lipids. hsCRP reduction was associated with less MCE, especially in patients with high baseline hsCRP. TRIAL REGISTRATION: NCT00092677.

Timing of surgery in asymptomatic aortic stenosis.

Prospective studies have convincingly shown that sudden death in asymptomatic patients with AS is rare and prognosis is good as long as LV function, exercise tolerance and exercise hemodynamics remain normal. The time interval to development of LV dysfunction is not known. Therefore the initial evaluation should be confirmed after 3-6 months including echocardiography and exercise testing to identify patients with rapid progression, LV dysfunction and other high risk patients in whom surgery can be expected to improve prognosis even if the patient remains asymptomatic.

Management of cardiovascular diseases during pregnancy.

The prevalence of cardiovascular diseases (CVDs) in women of childbearing age is rising. The successes in medical and surgical treatment of congenital heart disease have led to an increasing number of women at childbearing age presenting with problems of treated congenital heart disease. Furthermore, in developing countries and in immigrants from these countries, rheumatic valvular heart disease still plays a significant role in young women. Increasing age of pregnant women and increasing prevalence of atherosclerotic risk factors have led to an increase in women with coronary artery disease at pregnancy. Successful management of pregnancy in women with CVDs requires early diagnosis, a thorough risk stratification, and appropriate management by a multidisciplinary team of obstetricians, cardiologists, anesthesiologists, and primary care physicians. The following review is based on the recent European guidelines on the management of CVDs during pregnancy, which aim at providing concise and simple recommendations for these challenging problems.

Impact of obesity and nonobesity on grading the severity of aortic valve stenosis.

We tested the hypothesis that the disproportionate increase of body surface area in obesity may lead to the overestimation of aortic stenosis (AS) severity when the aortic valve area (AVA) is indexed (AVAI) for body surface area in 1,524 patients enrolled in the Simvastatin and Ezetimibe in AS study. Obesity was defined as a body mass index of ≥30 kg/m(2). Peak aortic jet velocity, mean aortic gradient, AVA, and energy loss (EL) did not differ, although AVAI and EL indexed (ELI) for body surface area were significantly smaller in the obese group (n = 321) compared with the nonobese (n = 1,203) group (both p <0.05). Severe AS by AVAI (<0.6 cm(2)/m(2)) but nonsevere by AVA (>1.0 cm(2); AVAI/AVA discordance) was found in 15% of the patients, whereas severe AS by ELI (<0.6 cm(2)/m(2)) but nonsevere by EL (>1.0 cm(2); ELI/EL discordance) was found in 9% of the patients. Obesity was associated with a 2.4-fold higher prevalence of AVAI/AVA discordance and a 1.6-fold higher prevalence of ELI/EL discordance. Discordant grading was also associated with male gender, larger body size, higher mean aortic gradient, and stroke volume (all p <0.05). During a median follow-up of 4.3 years, 419 patients were referred for aortic valve replacement and 177 patients died or were hospitalized because of heart failure. In the Cox regression analyses, AVAI/AVA discordance was associated with a 28% higher rate of aortic valve replacement (p <0.05) but did not predict the rate of combined death and hospitalization for heart failure. In conclusion, using AVAI and ELI for the grading of stenosis in patients with obesity may lead to overestimation of true AS severity.

Velocity ratio predicts outcomes in patients with low gradient severe aortic stenosis and preserved EF.

OBJECTIVE: To evaluate the usefulness of velocity ratio (VR) in patients with low gradient severe aortic stenosis (LGSAS) and preserved EF. BACKGROUND: LGSAS despite preserved EF represents a clinically challenging entity. Reliance on mean pressure gradient (MPG) may underestimate stenosis severity as has been reported in the context of paradoxical low flow, LGSAS. On the other hand, grading of stenosis severity by aortic valve area (AVA) may overrate stenosis severity due to erroneous underestimation of LV outflow tract (LVOT) diameter, small body size or inconsistencies in cut-off values for severe stenosis. We hypothesised that VR may have conceptual advantages over MPG and AVA, predict clinical outcomes and thereby be useful in the management of patients with LGSAS. METHODS: Patients from the prospective Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study with an AVA<1.0 cm(2), MPG≤40 mm Hg and EF≥55% and asymptomatic at baseline were stratified according to VR with a cut-off value of 0.25. Outcomes were evaluated according to aortic valve-related events and cardiovascular death. RESULTS: Of 435 patients with LGSAS, 197 (45%) had VR<0.25 suggesting severe and 238 (55%) had VR≥0.25 suggesting non-severe stenosis. Aortic valve-related events (mean follow-up 42±14 months) were more frequent in patients with VR<0.25 (57% vs 41%; p<0.001) as was cardiovascular death within the first 24 months (p<0.05). In multivariable Cox regression analysis, MPG was the strongest independent predictor of aortic valve events (p<0.001) followed by VR (p<0.02). Adjusting AVA by VR increased predictive accuracy for aortic valve events (area under the receiver operating curve 0.62 (95% CI 0.57 to 0.67) vs 0.56 (95% CI 0.51 to 0.61) for AVA, p=0.02) with net reclassification improvement calculated at 0.36 (95% CI 0.17 to 0.54, p<0.001). VR did not improve the prediction of clinical events by MPG. CONCLUSIONS: In the difficult setting of LGSAS, VR shows a strong association with valve-related events and-although not outperforming MPG-may be particularly useful in guiding clinical management. TRIAL REGISTRATION NUMBER: NCT00092677.

Indexing aortic valve area by body surface area increases the prevalence of severe aortic stenosis.

BACKGROUND: To account for differences in body size in patients with aortic stenosis, aortic valve area (AVA) is divided by body surface area (BSA) to calculate indexed AVA (AVAindex). Cut-off values for severe stenosis are <1.0 cm2 for AVA and <0.6 cm2/m2 for AVAindex. OBJECTIVE: To investigate the influence of indexation on the prevalence of severe aortic stenosis and on the predictive accuracy regarding clinical outcome. METHODS: Echocardiographic and anthropometric data from a retrospective cohort of 2843 patients with aortic stenosis (jet velocity >2.5 m/s) and from 1525 patients prospectively followed in the simvastatin and ezetimibe in aortic stenosis (SEAS) trial were analysed. RESULTS: The prevalence of severe stenosis increased with the AVAindex criterion compared to AVA from 71% to 80% in the retrospective cohort, and from 29% to 44% in SEAS (both p<0.001). Overall, the predictive accuracy for aortic valve events was virtually identical for AVA and AVAindex in the SEAS population (mean follow-up of 46 months; area under the receiver operating characteristic curve: 0.67 (95% CI 0.64 to 0.70) vs. 0.68 (CI 0.65 to 0.71) (NS). However, 213 patients additionally categorised as severe by AVAindex experienced significantly less valve related events than those fulfilling only the AVA criterion (p<0.001). CONCLUSIONS: Indexing AVA by BSA (AVAindex) significantly increases the prevalence of patients with criteria for severe stenosis by including patients with a milder degree of the disease without improving the predictive accuracy for aortic valve related events.