Diagnostic and Therapeutic Approaches for Heart Failure in Long-Term Survivors of Childhood Cancer.

The improvement in survival rates in pediatric malignancies has led to an increase in the number of cancer survivors who are at risk of developing cardiotoxicity and heart failure. Cardiac dysfunction in these patients can occur asymptomatically, and the diagnosis in a symptomatic phase is associated with reduced treatment response and worse prognosis. For this reason, it is essential to establish protocols to follow up on these patients and identify those at risk of cardiotoxicity in order to start early and effective therapies. This review aims to summarize the latest findings in the diagnosis and treatment of cancer therapy-related cardiac disease in long-term survivors of childhood cancer, with a focus on heart failure.

Letter to the Editor Ross procedure valve function, clinical outcomes and predictors after 25 years follow up.

The following letter presents an answer of a comment of our work titled "Ross procedure: valve function, clinical outcomes and predictors after 25 years' follow-up," recently published in your journal by Rangwala et al.1 As our colleagues point out, the Ross procedure has excellent survival rates but a significant risk of valve dysfunction and therefore reintervention at follow-up. Although the survival advantage with the Ross procedure appears to be consistent compared with mechanical valve substitutes, this benefit is not as clear compared with biological valve substitutes. However, biological valve substitutes also have significant reintervention rates during follow-up. The different surgical modifications of the Ross procedure have not clearly demonstrated better results in follow-up in terms of autograft reintervention. This procedure can be performed in a medium-volume center with good results as long as adequate patient selection and adequate surgical training are carried out.

Ross procedure: valve function, clinical outcomes and predictors after 25 years' follow-up.

OBJECTIVE: To describe long-term outcomes of the Ross procedure in a single center and retrospective series after 25 years follow-up. METHODS: From 1997-2019 we included all consecutive patients who underwent Ross procedure at our center. Clinical and echocardiographic evaluations were performed at least yearly. Echocardiographic valvular impairment was defined as at least moderate autograft or homograft dysfunction. Reintervention outcomes included surgical and percutaneous approach. RESULTS: 151 Ross procedures were performed (mean age 28±12years, 21 %<16years, 70 %male). After 25 years follow-up (median 18 years, interquartile range 9-21, only 3 patients lost) 12 patients died (8 %); Autograft, homograft or any valve dysfunction were present in 38(26 %), 48(32 %) and 75(51 %), respectively; and reintervention in 22(15%), 17(11%) and 38(26 %) respectively. At 20 years of follow-up, probabilities of survival free from autograft, homograft or any valve dysfunction were 63 %, 60 % and 35 %; and from reintervention, 80 %, 85 % and 67 %, respectively. The learning curve period (first 12 cases) was independently associated to autograft dysfunction (HR 2.78, 95 %CI:1.18-6.53, p = 0.02) and reintervention (HR 3.76, 95 %CI: 1.46-9.70, p = 0.006). Larger native pulmonary diameter was also an independent predictor of autograft reintervention (HR 1.22, 95 %CI:1.03-1.45, p = 0.03). Homograft dysfunction was associated with younger age (HR 5.35, 95 %CI: 2.13-13.47, p<0.001) and homograft reintervention, with higher left ventricle ejection fraction (HR 1,10, 95 %CI:1.02-1.19, p<0.02). CONCLUSIONS: In this 25 years' experience after the Ross procedure, global survival was high, although autograft and homograft dysfunction and reintervention rates were not negligible. Clinical and echocardiographic variables can identify patients with higher risk of events in follow up.

Diastolic function assessment with left atrial strain in long-term survivors of childhood acute lymphoblastic leukemia.

INTRODUCTION AND OBJECTIVES: Survivors of childhood cancer might be at increased risk of diastolic dysfunction at follow-up due to exposure to cardiotoxic treatment. Although assessment of diastolic function is challenging in this relatively young population, left atrial strain might provide a novel insight in this evaluation. Our aim was to examine diastolic function in a cohort of long-term survivors of childhood acute lymphoblastic leukemia by using left atrial strain and conventional echocardiographic parameters. METHODS: Long-term survivors who were diagnosed at a single center between 1985 and 2015 and a control group of healthy siblings were recruited. Conventional diastolic function parameters and atrial strain were compared, and the latter was measured during the 3 atrial phases: reservoir (PALS), conduit (LACS) and contraction (PACS). Inverse probability of treatment weighting was used to account for differences between the groups. RESULTS: We analyzed 90 survivors (age, 24.6±9.7 years, time since diagnosis 18 [11-26] years) and 58 controls. PALS and LACS were significantly reduced compared with the control group: 46.4±11.2 vs 52.1±11.7; P=.003 and 32.5±8.8 vs 38.2±9.3; P=.003, respectively. Conventional diastolic parameters and PACS were similar between the groups. The reductions in PALS and LACS were associated with exposure to cardiotoxic treatment in age- and sex-adjusted analysis (≥ moderate risk, low risk, controls): 45.4±10.5, 49.5±12.9, 52.1±11.7; Padj=.003, and 31.7±9.0, 35.2±7.5, 38.2±9.3; Padj=.001, respectively. CONCLUSIONS: Long-term childhood leukemia survivors showed a subtle impairment of diastolic function that was detected with atrial strain but not with conventional measurements. This impairment was more pronounced in those with higher exposure to cardiotoxic treatment.

Right Ventricular Function in Long-Term Survivors of Childhood Acute Lymphoblastic Leukemia: From the CTOXALL Study.

There are limited data regarding right ventricle (RV) impairment in long-term survivors of childhood acute lymphoblastic leukemia (CLS). The aim of this study was to assess RV function in these patients using echocardiographic conventional measurements and automated RV strain. Echocardiographic recordings of 90 CLS and 58 healthy siblings from the CTOXALL cohort were analyzed. For group comparisons, inverse probability weighting was used to reduce confounding. The CLS group (24.6 ± 9.7 years, 37.8% women) underwent an echocardiographic evaluation 18 (11-26) years after the diagnosis. RV systolic dysfunction was found in 16.7% of CLS individuals using RV free-wall strain (RVFWS) compared to 2.2 to 4.4% with conventional measurements. RV systolic function measurements were lower in the CLS than in the control group: TAPSE (23.3 ± 4.0 vs. 25.2 ± 3.4, p = 0.004) and RVFWS (24.9 ± 4.6 vs. 26.8 ± 4.7, p = 0.032). Modifiable cardiovascular risk factors such as obesity (p = 0.022) and smoking (p = 0.028) were independently associated with reduced RVFWS. In conclusion, RV systolic function impairment was frequent in long-term survivors of childhood leukemia, underscoring the importance of RV assessment, including RVFWS, in the cardiac surveillance of these patients.

Complications of the Percutaneous Mitral Valve Edge-To-Edge Repair: Role of Transesophageal Echocardiography.

The use of transcatheter edge-to-edge repair for the treatment of mitral regurgitation has markedly increased in the last few years. The rate of adverse events related to the procedure is low; however, some of the complications that may occur are potentially dangerous. Due to the growing popularity of the technique, which is no longer limited to high-volume centers, knowledge of the complications related to the procedure is fundamental. Transesophageal echocardiography has a key role in the guidance of the intervention while allowing for the avoidance of most of these adverse events, as well as enabling us to diagnose them early. In this article, we review the main complications that might present during a transcatheter mitral edge-to-edge repair procedure (tamponade, thromboembolic events, single leaflet device attachment, device embolization, vascular injury…) while highlighting key aspects of transesophageal echocardiographic monitoring in the prevention and prompt diagnosis of these complications.

Temporal trend and potential impact of angiotensin receptor neprilysin inhibitors on transcatheter edge-to-edge mitral valve repair.

INTRODUCTION AND OBJECTIVES: Transcatheter edge-to-edge repair (TEER) should be considered in patients with heart failure and secondary mitral regurgitation (MR). Angiotensin receptor-neprilysin inhibitors (ARNIs) have been demonstrated to improve prognosis in heart failure. We aimed to evaluate the impact ARNIs on patient selection and outcomes. METHODS: The population of the Spanish TEER prospective registry (March 2012 to January 2021) was divided into 2 groups: a) TEER before the ARNI era (n=450) and b) TEER after the recommendation of ARNIs by European Guidelines (n=639), with further analysis according to intake (n=52) or not (n=587) of ARNIs. RESULTS: A total of 1089 consecutive patients underwent TEER for secondary MR. In the ARNI era, there was a reduction in left ventricle dilation (82mL vs 100mL, P=.025), and better function (35% vs 38%, P=.011). At 2 years of follow-up, mortality (10.6% vs 17.3%, P <.001) and heart failure readmissions (16.6% vs 27.8%, P <.001) were lower in the ARNI era, but not recurrent MR. In the ARNI era, 1- and 2-year mortality were similar irrespective of ARNI intake but patients on ARNIs had a lower risk of readmission+mortality at 2 years (OR, 0.369; 95%CI, 0.137-0.992; P=.048), better NYHA class, and lower recurrence of MR III-IV (1.9% vs 14.3%, P=.011). CONCLUSIONS: Better patient selection for TEER has been achieved in the last few years with a parallel improvement in outcomes. The use of ARNIs was associated with a significant reduction in overall events, better NYHA class, and lower MR recurrence.

Automated Global Longitudinal Strain Assessment in Long-Term Survivors of Childhood Acute Lymphoblastic Leukemia.

There is limited evidence that supports the use of the global longitudinal strain (GLS) in long-term cardiac monitoring of childhood acute lymphoblastic leukemia survivors (CLSs). Our aim was to assess the utility of automated GLS to detect left ventricular systolic dysfunction (LVSD) in long-term CLSs. Asymptomatic and subclinical LVSD were defined as LVEF < 50% and GLS < 18.5%, respectively. Echocardiographic measurements and biomarkers were compared with a control group. Inverse probability weighting was used to reduce confounding. Regression models were used to identify factors associated with LVEF and GLS in the survivors. Ninety survivors with a median follow-up of 18 (11−26) years were included. The prevalence of LVSD was higher using GLS than with LVEF (26.6% vs. 12.2%). The measurements were both reduced as compared with the controls (p < 0.001). There were no differences in diastolic parameters and NT-ProBNP. Survivors were more likely to have Hs-cTnI levels above the detection limit (40% vs. 17.2%, p = 0.006). The dose of anthracycline was associated with LVEF but not with GLS in the survivors. Biomarkers were not associated with GLS or LVEF. In conclusion, LVSD detection using automated GLS was higher than with LVEF in long-term CLSs. Its incorporation into clinical routine practice may improve the surveillance of these patients.

Clinical and echocardiographic outcomes of transcatheter mitral valve repair in atrial functional mitral regurgitation.

BACKGROUND: Isolated atrial fibrillation can cause mitral regurgitation (MR) in patients with normal left ventricular systolic function and no organic disease of the mitral valve. Little information is available regarding outcomes of Mitraclip in patients with atrial functional mitral regurgitation (AFMR). We aimed to evaluate 12-month clinical and echocardiographic outcomes of transcatheter mitral valve repair (TMVR) with MitraClip in patients with AFMR compared to those with ventricular functional or degenerative/mixed MR. METHODS: Registry-based analysis of all consecutive patients who underwent TMVR and were included in the Spanish Registry of Mitraclip. Changes in MR and NYHA functional class, and a combined endpoint including all-cause mortality and hospitalizations due to heart failure were the main outcomes. RESULTS: Overall, 1074 (69.1% male, 73.3 ± 10.2 years-old) patients were analyzed in this report. 48 patients (4.5%) presented AFMR. AFMR was significantly reduced after TMVR, with a procedural success rate of 91.7%, and this reduction persisted at 12-month (p < 0.001). Patients with AFMR showed a significant functional improvement at 6- and 12-month follow-up in our series (baseline: NYHA III 70.8% IV 18.8% vs. 1-year: NYHA III 21.7% IV 0%; p < 0.001). The probability of survival free of readmission for heart failure and all-cause mortality within the first year after TMVR was 74.9%. Procedural and clinical outcomes, as well as recurrent rates of MR were similar acutely and at 1-year compared to other etiologies. CONCLUSION: TMVR in patients with AFMR showed no significant differences compared to ventricular functional or degenerative/mixed MR regarding MR reduction or clinical outcomes.

Prognostic Role of TAPSE to PASP Ratio in Patients Undergoing MitraClip Procedure.

BACKGROUND: Transcatheter mitral valve repair (TMVR) is an effective therapy for high-risk patients with severe mitral regurgitation (MR) but heart failure (HF) readmissions and death remain substantial on mid-term follow-up. Recently, right ventricular (RV) to pulmonary arterial (PA) coupling has emerged as a relevant prognostic predictor in HF. In this study, we aimed to assess the prognostic value of tricuspid annular plane systolic excursion (TAPSE) to PA systolic pressure (PASP) ratio as a non-invasive measure of RV-to-PA coupling in patients undergoing TMVR with MitraClip (Abbott, CA, USA). METHODS: Multicentre registry including 228 consecutive patients that underwent successful TMVR with MitraClip. The sample was divided in two groups according to TAPSE/PASP median value: 0.35. The primary combined endpoint encompassed HF readmissions and all-cause mortality. RESULTS: Mean age was 72.5 ± 11.5 years and 154 (67.5%) patients were male. HF readmissions and all-cause mortality were more frequent in patients with TAPSE/PASP ≤ 0.35: Log-Rank 8.844, p = 0.003. On Cox regression, TAPSE/PASP emerged as a prognostic predictor of the primary combined endpoint, together with STS-Score. TAPSE/PASP was a better prognostic predictor than either TAPSE or PASP separately. CONCLUSIONS: TAPSE/PASP ratio appears as a novel prognostic predictor in patients undergoing MitraClip implantation that might improve risk stratification and candidate selection.

Stratification and management of cardiovascular risk in cancer patients. A consensus document of the SEC, FEC, SEOM, SEOR, SEHH, SEMG, AEEMT, AEEC, and AECC.

Both cancer treatment and survival have significantly improved, but these advances have highlighted the deleterious effects of vascular complications associated with anticancer therapy. This consensus document aims to provide a coordinated, multidisciplinary and practical approach to the stratification, monitoring and treatment of cardiovascular risk in cancer patients. The document is promoted by the Working Group on Cardio Oncology of the Spanish Society of Cardiology (SEC) and was drafted in collaboration with experts from distinct areas of expertise of the SEC and the Spanish Society of Hematology and Hemotherapy (SEHH), the Spanish Society of Medical Oncology (SEOM), the Spanish Society of Radiation Oncology (SEOR), the Spanish Society of General and Family Physicians (SEMG), the Spanish Association of Specialists in Occupational Medicine (AEEMT), the Spanish Association of Cardiovascular Nursing (AEEC), the Spanish Heart Foundation (FEC), and the Spanish Cancer Association (AECC).

Acute Kidney Injury After Percutaneous Edge-to-Edge Mitral Repair.

BACKGROUND: In catheter-based procedures, acute kidney injury (AKI) is a frequent, serious complication ranging from 10% to 30%. In MitraClip (Abbott Vascular, Santa Clara, California), a usually contrast-free procedure, there is scarce data about its real incidence and impact. OBJECTIVES: This study aimed to evaluate incidence, predictive factors, and midterm outcomes of AKI in patients with significant mitral regurgitation (MR) undergoing transcatheter valve repair with MitraClip. METHODS: A total of 721 patients undergoing MitraClip were included. AKI was defined as an absolute or a relative increase in serum creatinine of >0.3 mg/dl or ≥50%, respectively, or the need for hemodialysis during index hospitalization. RESULTS: The mean age of the patients was 72 ± 11 years (28.3% women). Median estimated glomerular filtration rate (eGFR) was 43.7 ml/min/1.73 m2 (interquartile range: 30.9 to 60.1 ml/min/1.73 m2), and was <60 ml/min/1.73 m2 in 74.9% of the patients. AKI after MitraClip occurred in 106 patients (14.7%). Baseline hemoglobin (<11 g/dl) (odds ratio [OR]: 1.97; p = 0.003), urgent procedure (OR: 3.44; p = 0.003), and absence of device success (OR: 3.37; p < 0.001) were independent predictors of AKI. Patients with AKI had worse outcomes compared to those without AKI, including a higher proportion of in-hospital bleeding events (3.8% vs. 0.8%; p = 0.011), 2-year all-cause mortality (40.5% vs. 18.7%; p <0.001), and major adverse cardiac events (63.6% vs. 23.5%; p <0.001). Combination of AKI with significant residual MR after the procedure conferred even worst outcomes (2-year all-cause mortality 50.0% vs. 19.6%; p = 0.001, and major adverse cardiac events 70.0% vs. 18.9%; p < 0.001). CONCLUSIONS: Despite being a "zero-contrast" procedure, one-sixth of patients undergoing transcatheter mitral valve repair had AKI, linked to device failure or other severe conditions. The occurrence of AKI was associated with worse outcomes, highlighting the importance to detect and reduce this complication in high-risk population.

Transcatheter Mitral Repair for Functional Mitral Regurgitation According to Left Ventricular Function: A Real-Life Propensity-Score Matched Study.

BACKGROUND: Transcatheter mitral valve repair (TMVR) could improve survival in functional mitral regurgitation (FMR), but it is necessary to consider the influence of left ventricular ejection fraction (LVEF). Therefore, we compare the outcomes after TMVR with Mitraclip® between two groups according to LVEF. METHODS: In an observational registry study, we compared the outcomes in patients with FMR who underwent TMVR with and without LVEF <30%. The primary endpoint was the combined one-year all-cause mortality and unplanned hospital readmissions due to HF. The secondary end-points were New York Heart Association (NYHA) functional class and mitral regurgitation (MR) severity. Propensity-score matching was used to create two groups with the same baseline characteristics, except for baseline LVEF. RESULTS: Among 535 FMR eligible patients, 144 patients with LVEF <30% (group 1) and 144 with LVEF >30% (group 2) had similar propensity scores and were included in the analyses. The primary study endpoint was significantlly higher in group 1 (33.3% vs. 9.4%, p = 0.002). There was a maintained improvement in secondary endpoints without significant differences among groups. CONCLUSION: FMR patients with LVEF <30% treated with MitraClip® had higher mortality and readmissions than patients with LVEF ≥30% treated with the same device. However, both groups improved the NYHA functional class and MR severity.

Myocardial deformation and acute cellular rejection after heart transplantation: Impact of inter-vendor variability in diagnostic effectiveness.

PURPOSE: Our objective was to investigate the impact of inter-vendor variability in the ability of myocardial strain analysis to detect acute cellular rejection (ACR) in heart transplant recipients. METHODS: We performed serial echocardiographic examinations in 18 consecutive adult heart transplanted patients, in their first year post-transplantation, within 3 hours of the routine surveillance endomyocardial biopsies (EMB) in a single center. Myocardial strain was analyzed using two software in two different institutions, and inter-vendor variability of strain values and its association with ACR (any grade or grade ≥2R) was investigated. The parameter of comparison was the peak value of the average curve of strain during the entire cardiac cycle. RESULTS: A total of 147 pairs of EMB-echocardiogram were performed, 65 with no ACR, 63 with ACR grade 1R, and 19 with ACR grade ≥2R. Intra-class correlation coefficients for left ventricle longitudinal, radial, and circumferential strain were 0.38, 0.39, and 0.77, respectively, and 0.32 for right ventricular longitudinal strain. Neither software found significant association of left ventricular longitudinal strain with rejection. Grade ≥2R ACR was associated with left ventricular circumferential strain measured with the first software and with left ventricular radial strain with the other; and ACR of any grade was only significantly associated with right ventricle longitudinal strain measured with the first software. CONCLUSIONS: Inter-vendor reproducibility of strain values was low in this study. Some strain parameters were associated to ACR, although these results were inconsistent between two commercially available software. Specific validation of each software is warranted for this clinical indication.

Sustained Improvement of Left Ventricular Strain following Transcatheter Aortic Valve Replacement.

PURPOSE: Left ventricular (LV) mechanics are impaired in patients with severe aortic stenosis (AS). Transcatheter aortic valve replacement (TAVR) has become a widespread technique for patients with severe AS considered inoperable or high risk for open surgery. This procedure could have a positive impact in LV mechanics. The aim of the study was to evaluate the effect of TAVR on LV function recovery, as assessed by myocardial deformation parameters, both immediately and in the long term. METHODS: One-hundred nineteen consecutive patients (81.2 ± 6.9 years, 50.4% female) from 10 centres in Europe with severe AS who successfully underwent TAVR with either a self-expanding CoreValve (Medtronic, Minneapolis, MN, USA) or a mechanically expanded Lotus valve (Boston Scientific, Natick, MA, USA) were enrolled in a prospective observational study. A complete echocardiographic examination was performed prior to device implantation, before discharge and 1 year after the procedure, including the assessment of LV strain using standard 2D images. RESULTS: Between baseline and discharge, only a modest but statistically significant improvement in GLS (global longitudinal strain) could be seen (GLS% -14.6 ± 5.0 at baseline; -15.7 ± 5.1 at discharge, p = 0.0116), although restricted to patients in the CoreValve group; 1 year after the procedure, a greater improvement in GLS was observed (GLS% -17.1 ± 4.9, p < 0.001), both in the CoreValve and the Lotus groups. CONCLUSIONS: Immediate and sustained improvement in GLS was appreciated after the TAVR procedure. Whether this finding continues to be noted in a more prolonged follow-up and its clinical implications need to be assessed in further studies.

Immediate improvement of left ventricular mechanics following transcatheter aortic valve replacement.

BACKGROUND: Left ventricular (LV) mechanics are impaired in patients with severe aortic stenosis (AS). Transcatheter aortic valve replacement (TAVR) has become a widespread technique for patients with severe AS considered inoperable or high risk for traditional open-surgery. This procedure could have a positive impact in LV mechanics. The aim of this study was to evaluate the immediate effect of TAVR on LV function recovery, as assessed by myocardial deformation parameters. METHODS: One-hundred twelve consecutive patients (81.4 ± 6.4 years, 50% female) from 10 centres in Europe with severe AS who successfully underwent TAVR with either a self-expanding CoreValve (Medtronic, Minneapolis, MN) or a mechanically expanded Lotus valve (Boston Scientific, Natick, MA) were enrolled in a prospective multi-center study. A complete echocardiographic examination was performed at baseline and immediately before discharge, including the assessment of LV strain using standard two-dimensional images. RESULTS: Echocardiographic examination with global longitudinal strain (GLS) quantification could be obtained in 92 patients, because of echocardiographic and logistic reasons. Between examinations, a modest statistically significant improvement in GLS could be seen (GLS% -15.00 ± 4.80 at baseline;-16.15 ± 4.97 at discharge, p = 0.028). In a stratified analysis, only women showed a significant improvement in GLS and a trend towards greater improvement in GLS according to severity of systolic dysfunction as measured by LV ejection fraction could be noted. CONCLUSIONS: Immediate improvement in GLS was appreciated after TAVR procedure. Whether this finding continues to be noted in a more prolonged follow-up and its clinical implications need to be assessed in further studies.

Overview of mitral regurgitation in Europe: results from the European Registry of mitral regurgitation (EuMiClip).

Aims: To determine the prevalence of mitral regurgitation (MR) in a large cohort of consecutive patients undergoing clinically indicated echocardiography and to examine the distribution of primary and secondary MR. Methods and results: All patients undergoing an echocardiographic study in 19 European centres within a 3-month period were prospectively included. MR assessment was performed as recommended by the European Association of Cardiovascular Imaging (EACVI). MR was classified according to mechanism as primary or secondary and aetiologies were reported. A total of 63 463 consecutive echocardiographic studies were reviewed. Any degree of MR was described in 15 501 patients. Concomitant valve disease of at least moderate grade was present in 28.5% of patients, being tricuspid regurgitation the most prevalent. In the subgroup of moderate and severe MR (n = 3309), 55% of patients had primary MR and 30% secondary MR. Both mechanisms were described in 14% of the studies. According to Carpentier's classification, 26.7% of MR were classified as I, 19.9% of MR as II, 22.4% of MR as IIIa, and 31.1% of MR as IIIb. Conclusion: To date, this is the largest echocardiography-based study to analyse the prevalence and aetiology distribution of MR in Europe. The burden of secondary MR was higher than previously described, representing 30% of patients with significant MR. In our environment, degenerative disease is the most common aetiology of primary MR (60%), whereas ischaemic is the most common aetiology of secondary MR (51%). Up to 70% of patients with severe primary MR may have a Class I indication for surgery. However, the optimal therapeutic approach for secondary MR remains uncertain.

Selección de lo mejor del año 2017 en imagen cardiovascular en el intervencionismo estructural / Selection of the best of 2017 in cardiac imaging and structural interventionism

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Large-scale assessment of aortic stenosis: facing the next cardiac epidemic?

Aims: Aortic stenosis (AS) is the most frequent valvular disease in developed countries. As society grows older, the prevalence of AS increases. However, the real burden, current aetiology, severity distribution, and echocardiographic patterns of AS are not fully clear. The aim of the present study is to provide an accurate overall picture of AS, focusing on its epidemiology, aetiology, and echocardiographic features. Methods and results: A total of 29 502 consecutive echocardiograpies were prospectively included in this multicentre study. The present sample was composed of patients with advanced age (mean 75.2 years) and similar gender distribution. High proportion (7.2%) showed any grade of AS, with important number of patients (2.8%) presenting severe AS, most of them aged 75 years or more. Coexisting valvular disease appeared in almost half of the sample (49.6%), being the most frequently diagnosed aortic regurgitation (AR) (22%) followed by mitral regurgitation (MR) (15.6%). Degenerative aetiology was found in the vast majority (93.4%) of the studies whereas rheumatic is currently infrequent (3.35%). Low flow-low gradient (LFLG) appeared in 24.6% of patients with severe AS. Atrial fibrillation (23.1% vs. 11.6%; P = 0.002), MR (23.3% vs. 15.1%; P = 0.018), and right ventricle dysfunction (13.3% vs. 5.2%; P = 0.003) appeared frequently in LFLG group. Conclusions: Burden of AS is higher than previously assumed. Degenerative aetiology is the main cause of AS. Most of the patients are elder with high prevalence of significant co-existing valvular disease. LFLG severe AS is present in an important proportion of patients, showing high grade of left ventricle remodelling.