Contemporary Presentation and Management of Valvular Heart Disease: The EURObservational Research Programme Valvular Heart Disease II Survey.

BACKGROUND: Valvular heart disease (VHD) is an important cause of mortality and morbidity and has been subject to important changes in management. The VHD II survey was designed by the EURObservational Research Programme of the European Society of Cardiology to analyze actual management of VHD and to compare practice with guidelines. METHODS: Patients with severe native VHD or previous valvular intervention were enrolled prospectively across 28 countries over a 3-month period in 2017. Indications for intervention were considered concordant if the intervention was performed or scheduled in symptomatic patients, corresponding to Class I recommendations specified in the 2012 European Society of Cardiology and in the 2014 American Heart Association/American College of Cardiology VHD guidelines. RESULTS: A total of 7247 patients (4483 hospitalized, 2764 outpatients) were included in 222 centers. Median age was 71 years (interquartile range, 62-80 years); 1917 patients (26.5%) were ≥80 years; and 3416 were female (47.1%). Severe native VHD was present in 5219 patients (72.0%): aortic stenosis in 2152 (41.2% of native VHD), aortic regurgitation in 279 (5.3%), mitral stenosis in 234 (4.5%), mitral regurgitation in 1114 (21.3%; primary in 746 and secondary in 368), multiple left-sided VHD in 1297 (24.9%), and right-sided VHD in 143 (2.7%). Two thousand twenty-eight patients (28.0%) had undergone previous valvular intervention. Intervention was performed in 37.0% and scheduled in 26.8% of patients with native VHD. The decision for intervention was concordant with Class I recommendations in symptomatic patients with severe single left-sided native VHD in 79.4% (95% CI, 77.1-81.6) for aortic stenosis, 77.6% (95% CI, 69.9-84.0) for aortic regurgitation, 68.5% (95% CI, 60.8-75.4) for mitral stenosis, and 71.0% (95% CI, 66.4-75.3) for primary mitral regurgitation. Valvular interventions were performed in 2150 patients during the survey; of them, 47.8% of patients with single left-sided native VHD were in New York Heart Association class III or IV. Transcatheter procedures were performed in 38.7% of patients with aortic stenosis and 16.7% of those with mitral regurgitation. CONCLUSIONS: Despite good concordance between Class I recommendations and practice in patients with aortic VHD, the suboptimal number in mitral VHD and late referral for valvular interventions suggest the need to improve further guideline implementation.

Standardized Definition of Structural Valve Degeneration for Surgical and Transcatheter Bioprosthetic Aortic Valves.

Bioprostheses are prone to structural valve degeneration, resulting in limited long-term durability. A significant challenge when comparing the durability of different types of bioprostheses is the lack of a standardized terminology for the definition of a degenerated valve. This issue becomes especially important when we try to compare the degeneration rate of surgically inserted and transcatheter bioprosthetic valves. This document, by the VIVID (Valve-in-Valve International Data), proposes practical and standardized definitions of valve degeneration and provides recommendations for the timing of clinical and imaging follow-up assessments accordingly. Its goal is to improve the quality of research and clinical care for patients with deteriorated bioprostheses by providing objective and strict criteria that can be utilized in future clinical trials. We hope that the adoption of these criteria by both the cardiological and surgical communities will lead to improved comparability and interpretation of durability analyses.

Educational needs and application of guidelines in the management of patients with mitral regurgitation. A European mixed-methods study.

Aims: To assess the knowledge and application of European Society of Cardiology (ESC) Guidelines in the management of mitral regurgitation (MR). Methods and results: A mixed-methods educational needs assessment was performed. Following a qualitative phase (interviews), an online survey was undertaken using three case scenarios (asymptomatic severe primary MR, symptomatic severe primary MR in the elderly, and severe secondary MR) in 115 primary care physicians (PCPs), and 439 cardiologists or cardiac surgeons from seven European countries. Systematic cardiac auscultation was performed by only 54% of clinicians in asymptomatic patients. Cardiologists appropriately interpreted echocardiographic assessment of mechanism and quantification of primary MR (≥75%), but only 44% recognized secondary MR as severe. In asymptomatic severe primary MR with an indication for surgery, 27% of PCPs did not refer the patient to a cardiologist and medical therapy was overused by 19% of cardiologists. In the elderly patient with severe symptomatic primary MR, 72% of cardiologists considered mitral intervention (transcatheter edge-to-edge valve repair in 72%). In severe symptomatic secondary MR, optimization of medical therapy was advised by only 51% of PCPs and 33% of cardiologists, and surgery considered in 30% of cases (transcatheter edge-to-edge repair in 64%). Conclusion: Systematic auscultation is underused by PCPs for the early detection of MR. Medical therapy is overused in primary MR and underused in secondary MR. Indications for interventions are appropriate in most patients with primary MR, but are unexpectedly frequent for secondary MR. These gaps identify important targets for future educational programs.

Outcomes of Surgery for Severe Aortic Regurgitation with Systolic Left Ventricular Dysfunction.

BACKGROUND AND AIM OF THE STUDY: Management of patients with aortic regurgitation (AR) and severe impairment of left ventricular (LV) function characterized by an ejection fraction (EF) ≤35% is challenging. Conflicting results regarding perioperative and long-term survival of these patients have been reported. The study aim was to compare in-hospital outcomes and long-term survival of patients with AR and severe LV dysfunction versus moderate dysfunction (35% 70 years and NYHA class III/IV symptoms were predictive of survival. CONCLUSIONS: In-hospital and long-term survival was similar in patients with severe LV dysfunction and with preserved or moderately reduced LV function. Positive reverse LV remodelling and improved LV function was evident at the two-year echocardiographic follow up in these patients, who should not be denied aortic valve surgery.

ESC Working Group on Valvular Heart Disease position paper--heart valve clinics: organization, structure, and experiences.

BACKGROUND: With an increasing prevalence of patients with valvular heart disease (VHD), a dedicated management approach is needed. The challenges encountered are manifold and include appropriate diagnosis and quantification of valve lesion, organization of adequate follow-up, and making the right management decisions, in particular with regard to the timing and choice of interventions. Data from the Euro Heart Survey have shown a substantial discrepancy between guidelines and clinical practice in the field of VHD and many patients are denied surgery despite having clear indications. The concept of heart valve clinics (HVCs) is increasingly recognized as the way to proceed. At the same time, very few centres have developed such expertise, indicating that specific recommendations for the initial development and subsequent operating requirements of an HVC are needed. AIMS: The aim of this position paper is to provide insights into the rationale, organization, structure, and expertise needed to establish and operate an HVC. Although the main goal is to improve the clinical management of patients with VHD, the impact of HVCs on education is of particular importance: larger patient volumes foster the required expertise among more senior physicians but are also fundamental for training new cardiologists, medical students, and nurses. Additional benefits arise from research opportunities resulting from such an organized structure and the delivery of standardized care protocols. CONCLUSION: The growing volume of patients with VHD, their changing characteristics, and the growing technological opportunities of refined diagnosis and treatment in addition to the potential dismal prognosis if overlooked mandate specialized evaluation and care by dedicated physicians working in a specialized environment that is called the HVC.

Long-term outcome of bicuspid aortic valve disease.

AIMS: Bicuspid aortic valve (BAV) is a common congenital condition that is frequently associated with aortic stenosis (AS) and aortic regurgitation (AR), as well as aortic aneurysms, but specific outcome data are scarce. The present study sought to assess outcomes in a large cohort of consecutive patients with BAV. METHODS AND RESULTS: A total of 581 consecutive patients (median age 29 years, 157 female) with BAV were included in the study and followed prospectively in a heart valve clinic follow-up programme. The overall survival rate after 10 years was 94.5%. During follow-up, 158 patients developed an indication for surgery. Event-free survival rates were 97%, 94%, 87%, and 73% at 1, 2, 5, and 10 years, respectively. In the multivariable analysis, event rates were independently predicted by AS [subdistribution hazard ratio (SHR) 2.3 per degree of severity], AR (SHR 1.5 per degree of severity), baseline aortic dilatation ≥ 40 mm (SHR 1.9), and age (SHR 1.3) (P < 0.001). CONCLUSION: BAV disease is associated with a high rate of cardiac events, but state-of-the-art care results in good survival with low rates of infective endocarditis, aortic dissection, and sudden death. Incremental degrees of AS and regurgitation, the presence of aortic dilatation, and age are predictive of cardiac events.

Republished: drug-induced valvular heart disease.

Drug-induced valvular heart disease (DIVHD) was first described in the 1960s. Initially, associations with ergot derivatives used for migraine prevention, or with anorectic drugs, were described. Drugs used for the treatment of Parkinson's disease and endocrine diseases, like hyperprolactinemia, may also induce VHD. More recently, the use of 3,4-methylendioxymetamphetamine (MDMA, 'Ecstasy') and benfluorexhave been found to be associated with DIVHD. Although some of these drugs were withdrawn from the market, several cases of patients requiring valve surgery even years after the cessation of therapy have been reported. DIVHD is not infrequent, may be severe, and has been described in association with several drugs. Even after drug cessation, long-term implications of this type of VHD may persist. The present review underlines the need for a careful evaluation of the associated clinical and echocardiographic risk factors to allow early recognition so as not to delay appropriate management.

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.

Left atrial size predicts outcome in severe but asymptomatic mitral regurgitation.

Patients with severe asymptomatic primary mitral regurgitation (MR) can be safely managed with an active surveillance strategy. Left atrial (LA) size is affected by MR severity, left ventricular function and is also associated with the risk of atrial fibrillation and may be an integrative parameter for risk stratification. The present study sought to determine the predictive value of LA size in a large series of asymptomatic patients with severe MR. 280 consecutive patients (88 female, median age 58 years) with severe primary MR and no guideline-based indications for surgery were included in a follow-up program until criteria for mitral surgery were reached. Event-free survival was determined and potential predictors of outcome were assessed. Survival free of any indication for surgery was 78% at 2 years, 52% at 6 years, 35% at 10 years and 19% at 15 years, respectively. Left atrial (LA) diameter was the strongest independent echocardiographic predictor of event-free survival with incremental predictive value for the thresholds of 50, 60 and 70 mm, respectively. In a multivariable analysis that encompassed age at baseline, previous history of atrial fibrillation, left ventricular end systolic diameter), LA diameter, sPAP > 50 mmHg and year of inclusion, LA diameter was the strongest independent echocardiographic predictor of event-free survival (adjusted HR = 1.039, p < 0.001). LA size is a simple and reproducible predictor of outcome in asymptomatic severe primary MR. In particular, it may help to identify patients who may benefit from early elective valve surgery in heart valve centers of excellence.

The multidisciplinary Heart Team approach for patients with cardiovascular disease: a step towards personalized medicine.

AIMS: Despite general agreement on the benefits of the Heart Team approach for patients with cardiac diseases, few data are available on its real impact on the decision-making process. The aim of the study is to define the evolution over time of the level of agreement with the systematic discussion of patients in the Heart Team and to evaluate the adherence to the Heart Team recommendations and the impact of the Heart Team on the clinical outcome of the patients. METHODS: In 2015--2016, an experienced cardiac surgeon and a cardiologist independently reviewed clinical data of a series of 100 patients (Group 1, G1) and subsequently for each patient recommended treatment (surgical, percutaneous, hybrid or medical therapy) or further diagnostic investigations. The next day, each case was discussed by the Hospital Heart Team. The Heart Team recommendation, the subsequent treatment received by the patient and the in-hospital outcome were recorded. The same study procedure was repeated in 2017 in a second (G2) and in 2018 in a third (G3) group, both of them including 100 patients. RESULTS: Complete agreement in treatment selection by the cardiac surgeon, cardiologist and the Heart Team was observed in 43% of cases in G1 and in 70% and 68% in G2 and G3, respectively (G1 vs. G2: P  < 0.001, G1 vs. G3: P  = 0.01, G2 vs. G3: P  = 0.30). Agreement was less frequent in patients with a higher risk profile and in patients with aortic valve stenosis. The Heart Team decision was implemented in 95% of cases with a 30-day mortality of 0.67%. CONCLUSION: Agreement in treatment selection among the cardiac surgeon, cardiologist and Heart Team appears to be low in the initial experience. Subsequently, it seems to steadily increase over time up to a limit, when it reaches a plateau of stable results. Heart Team clinical cases discussion, based on both guidelines and multidisciplinary experience, represents a key step in defining the best patient treatment pathway, potentially improving the decision-making process and clinical results.

A streamlined, machine learning-derived approach to risk-stratification in heart failure patients with secondary tricuspid regurgitation.

AIMS: Secondary tricuspid regurgitation (sTR) is the most frequent valvular heart disease and has a significant impact on mortality. A high burden of comorbidities often worsens the already dismal prognosis of sTR, while tricuspid interventions remain underused and initiated too late. The aim was to examine the most powerful predictors of all-cause mortality in moderate and severe sTR using machine learning techniques and to provide a streamlined approach to risk-stratification using readily available clinical, echocardiographic and laboratory parameters. METHODS AND RESULTS: This large-scale, long-term observational study included 3359 moderate and 1509 severe sTR patients encompassing the entire heart failure spectrum (preserved, mid-range and reduced ejection fraction). A random survival forest was applied to investigate the most important predictors and group patients according to their number of adverse features.The identified predictors and thresholds, that were associated with significantly worse mortality were lower glomerular filtration rate (<60 mL/min/1.73m2), higher NT-proBNP, increased high sensitivity C-reactive protein, serum albumin < 40 g/L and hemoglobin < 13 g/dL. Additionally, grouping patients according to the number of adverse features yielded important prognostic information, as patients with 4 or 5 adverse features had a fourfold risk increase in moderate sTR [4.81(3.56-6.50) HR 95%CI, P < 0.001] and fivefold risk increase in severe sTR [5.33 (3.28-8.66) HR 95%CI, P < 0.001]. CONCLUSION: This study presents a streamlined, machine learning-derived and internally validated approach to risk-stratification in patients with moderate and severe sTR, that adds important prognostic information to aid clinical-decision-making.

Serum glutathione S-transferase P1 1 in prediction of cardiac function.

BACKGROUND: Glutathione S-transferase P1 1 (GSTP1) belongs to the multigene isozyme family involved in cellular response to oxidative stress and apoptosis. Our initial retrospective proteomic analysis suggested that GSTP1 is associated with heart failure (HF). Although pro-B-type natriuretic peptide (proBNP) serves currently as a surrogate diagnostic and prognostic parameter in HF patients, its specificity remains uncertain. We hypothesized that GSTP1 might be a useful serum marker in the monitoring of HF patients. METHODS AND RESULTS: Serum GSTP1 and proBNP were prospectively measured in 193 patients subdivided based on their ejection fraction (EF) either in equal-sized quintiles or predefined EF groups >52%, 43%-52%, 33%-42%, 23%-32% and ≤22%. At a cutoff of ≥231 ng/mL, GSTP1 identified HF patients with EF ≤22% with 81% sensitivity and 83% specificity, and at a cutoff of ≥655 pg/mL, proBNP identified the same patient group with 84% sensitivity and 22% specificity. GSTP1 at a ≥126 ng/mL cutoff identified EF ≤42% with 90% sensitivity and 95% specificity, or proBNP at a ≥396 pg/mL cutoff had 97% sensitivity and 20% specificity. In regression analyses, GSTP1, but not proBNP, discriminated between EF ≤42% and EF >42% in HF patients. CONCLUSIONS: These results suggest that GSTP1 is strongly associated with HF and could serve as a sensitive and specific marker to predict the ventricular function in HF patients.

Benefit of atrial septal defect closure in adults: impact of age.

AIMS: To evaluate the effect of age on the clinical benefit of atrial septal defect (ASD) closure in adults. METHODS AND RESULTS: Functional status, the presence of arrhythmias, right ventricular (RV) remodelling, and pulmonary artery pressure (PAP) were studied in 236 consecutive patients undergoing transcatheter ASD closure [164 females, mean age of 49 ± 18 years, 78 younger than 40 years (Group A), 84 between 40 and 60 years (Group B) and 74 older than 60 years (Group C)]. Defect size [median 22 mm (inter-quartile range, 19, 26 mm)] and shunt ratio [Qp:Qs 2.2 (1.7, 2.9)] did not differ among age groups. Older patients had, however, more advanced symptoms and both, PAP (r = 0.65, P < 0.0001) and RV size (r = 0.28, P < 0.0001), were significantly related to age. Post-interventionally, RV size decreased from 41 ± 7, 43 ± 7, and 45 ± 6 mm to 32 ± 5, 34 ± 5, and 37 ± 5 mm for Groups A, B, and C, respectively (P < 0.0001), and PAP decreased from 31 ± 7, 37 ± 10, and 53 ± 17 mmHg to 26 ± 5, 30 ± 6, and 43 ± 14 mmHg (P < 0.0001), respectively. Absolute changes in RV size (P = 0.80) and PAP (P = 0.24) did not significantly differ among groups. Symptoms were present in 13, 49, and 83% of the patients before and in 3, 11, and 34% after intervention in Groups A, B, and C. Functional status was related to PAP. CONCLUSIONS: At any age, ASD closure is followed by symptomatic improvement and regression of PAP and RV size. However, the best outcome is achieved in patients with less functional impairment and less elevated PAP. Considering the continuous increase in symptoms, RV remodelling, and PAP with age, ASD closure must be recommended irrespective of symptoms early after diagnosis even in adults of advanced age.

Guideline directed medical therapy and reduction of secondary mitral regurgitation.

BACKGROUND: Guideline-directed medical therapy (GDMT) is the recommended initial treatment for secondary mitral regurgitation (SMR), however, supported by only little comprehensive evidence. This study, therefore, sought to assess the effect of GDMT titration on SMR and to identify specific substance combinations able to reduce SMR severity. METHODS AND RESULTS: We included 261 patients who completed two visits with an echocardiographic exam available within 1 month at each visit. After comprehensively defining GDMT titration as well as SMR reduction, logistic regression analysis was applied in order to assess the effects of overall GDMT titration and specific substance combinations on SMR severity. SMR severity improved by at least 1° in 39.3% of patients with subsequent titration of GDMT and was accompanied by reverse remodelling and clinical improvement. The effects of GDMT titration were significantly associated with SMR reduction (adj. odds ratio 2.91, 95% confidence interval 1.34-6.32, P = 0.007). Moreover, angiotensin receptor/neprilysin inhibitor (ARNi) as well as the combined dosage effects of (i) renin-angiotensin system inhibitors (RASi) and mineralocorticoid-receptor antagonists (MRA), (ii) beta-blockers (BB) and MRA, as well as (iii) RASi, BB, and MRA were all significantly associated with SMR improvement (P < 0.044 for all). CONCLUSION: The present study provides comprehensive evidence for the effectiveness of contemporary GDMT to specifically improve SMR. Our data indicate that GDMT titration conveys a three-fold increased chance of reducing SMR severity. Moreover, the dosage effects of ARNi, as well as the combination of RASi and MRA, BB and MRA, and all three substances in the aggregate are able to significantly improve SMR.

Tailored Risk Stratification in Severe Mitral Regurgitation and Heart Failure Using Supervised Learning Techniques.

Background: Secondary mitral regurgitation (sMR) in the setting of heart failure (HF) has considerable impact on quality of life, HF rehospitalizations, and mortality. Identification of high-risk cohorts is essential to understand disease trajectories and for risk stratification. Objectives: This study aimed to provide a structured decision tree-like approach to risk stratification in patients with severe sMR and HF. Methods: This observational study included 1,317 patients with severe sMR from the entire HF spectrum. Clinical, echocardiographic, and laboratory data were extracted for all patients. The primary end point was all-cause mortality. Survival tree analysis, a supervised learning technique, was applied to identify patient subgroups at risk of mortality and further stratified by HF subtype (preserved, mildly reduced, and reduced ejection fraction). Results: Using supervised learning (survival tree method), 8 distinct subgroups were identified that differed significantly in long-term survival. Subgroup 7, characterized by younger age (≤66 years), higher hemoglobin (>12.7 g/dL), and higher albumin levels (>40.6 g/L) had the best survival. In contrast, subgroup 5 displayed a 20-fold risk of mortality (hazard ratio: 20.38 [95% CI: 10.78-38.52]); P < 0.001 and had older age (>68 years), low serum albumin (≤40.6 g/L), and higher NT-proBNP levels (≥9,750 pg/mL). Unique subgroups were further identified for each type of HF subtypes. Conclusions: Supervised machine learning reveals heterogeneity in the sMR risk spectrum, highlighting the clinical variability in the population. A decision tree-like model can help identify differences in outcomes among subgroups and can help provide tailored risk stratification.

Reverse Remodeling Following Valve Replacement in Coexisting Aortic Stenosis and Transthyretin Cardiac Amyloidosis.

BACKGROUND: Dual pathology of severe aortic stenosis (AS) and transthyretin cardiac amyloidosis (ATTR) is increasingly recognized. Evolution of symptoms, biomarkers, and myocardial mechanics in AS-ATTR following valve replacement is unknown. We aimed to characterize reverse remodeling in AS-ATTR and compared with lone AS. METHODS: Consecutive patients referred for transcatheter aortic valve replacement (TAVR) underwent ATTR screening by blinded 99mTc-DPD bone scintigraphy (Perugini Grade-0 negative, 1-3 increasingly positive) before intervention. ATTR was diagnosed by DPD and absence of monoclonal protein. Reverse remodeling was assessed by comprehensive evaluation before TAVR and at 1 year. RESULTS: One hundred twenty patients (81.8±6.3 years, 51.7% male, 95 lone AS, 25 AS-ATTR) with complete follow-up were studied. At 12 months (interquartile range, 7-17) after TAVR, both groups experienced significant symptomatic improvement by New York Heart Association functional class (both P<0.001). Yet, AS-ATTR remained more symptomatic (New York Heart Association ≥III: 36.0% versus 13.8; P=0.01) with higher residual NT-proBNP (N-terminal pro-brain natriuretic peptide) levels (P<0.001). Remodeling by echocardiography showed left ventricular mass regression only for lone AS (P=0.002) but not AS-ATTR (P=0.5). Global longitudinal strains improved similarly in both groups. Conversely, improvement of regional longitudinal strain showed a base-to-apex gradient in AS-ATTR, whereas all but apical segments improved in lone AS. This led to the development of an apical sparing pattern in AS-ATTR only after TAVR. CONCLUSIONS: Patterns of reverse remodeling differ from lone AS to AS-ATTR, with both groups experiencing symptomatic improvement by TAVR. After AS treatment, AS-ATTR transfers into a lone ATTR cardiomyopathy phenotype.

Natural history of very severe aortic stenosis.

BACKGROUND: We sought to assess the outcome of asymptomatic patients with very severe aortic stenosis. METHODS AND RESULTS: We prospectively followed 116 consecutive asymptomatic patients (57 women; age, 67 + or - 16 years) with very severe isolated aortic stenosis defined by a peak aortic jet velocity (AV-Vel) > or = 5.0 m/s (average AV-Vel, 5.37 + or - 0.35 m/s; valve area, 0.63 + or - 0.12 cm(2)). During a median follow-up of 41 months (interquartile range, 26 to 63 months), 96 events occurred (indication for aortic valve replacement, 90; cardiac deaths, 6). Event-free survival was 64%, 36%, 25%, 12%, and 3% at 1, 2, 3, 4, and 6 years, respectively. AV-Vel but not aortic valve area was shown to independently affect event-free survival. Patients with an AV-Vel > or = 5.5 m/s had an event-free survival of 44%, 25%, 11%, and 4% at 1, 2, 3, and 4 years, respectively, compared with 76%, 43%, 33%, and 17% for patients with an AV-Vel between 5.0 and 5.5 m/s (P<0.0001). Six cardiac deaths occurred in previously asymptomatic patients (sudden death, 1; congestive heart failure, 4; myocardial infarction, 1). Patients with an initial AV-Vel > or = 5.5 m/s had a higher likelihood (52%) of severe symptom onset (New York Heart Association or Canadian Cardiovascular Society class >II) than those with an AV-Vel between 5.0 and 5.5 m/s (27%; P=0.03). CONCLUSIONS: Despite being asymptomatic, patients with very severe aortic stenosis have a poor prognosis with a high event rate and a risk of rapid functional deterioration. Early elective valve replacement surgery should therefore be considered in these patients.