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BACKGROUND: Current cardiovascular prevention strategies are based on studies that seldom include valvular heart disease (VHD). The role of modifiable lifestyle factors on VHD progression and life expectancy among the elderly with different socioeconomic statuses (SES) remains unknown. METHODS: This cohort study included 164,775 UK Biobank participants aged 60 years and older. Lifestyle was determined using a five-factor scoring system covering smoking status, obesity, physical activity, diet, and sleep patterns. Based on this score, participants were then classified into "poor," "moderate," or "ideal" lifestyle groups. SES was classified as high or low based on the Townsend Deprivation Index. The association of lifestyle with major VHD progression was evaluated using a multistate mode. The life table method was employed to determine life expectancy with VHD and without VHD. RESULTS: The UK Biobank documented 5132 incident VHD cases with a mean follow-up of 12.3 years and 1418 deaths following VHD with a mean follow-up of 6.0 years. Compared to those with a poor lifestyle, women and men followed an ideal lifestyle had lower hazard ratios for incident VHD (0.66 with 95% CI, 0.59-0.73 for women and 0.77 with 95% CI, 0.71-0.83 for men) and for post-VHD mortality (0.58 for women, 95% CI 0.46-0.74 and 0.62 for men, 95% CI 0.54-0.73). When lifestyle and SES were combined, the lower risk of incident VHD and mortality were observed among participants with an ideal lifestyle and high SES compared to participants with an unhealthy lifestyle and low SES. There was no significant interaction between lifestyle and SES in their correlation with the incidence and subsequent mortality of VHD. Among low SES populations, 60-year-old women and men with VHD who followed ideal lifestyles lived 4.2 years (95% CI, 3.8-4.7) and 5.1 years (95% CI, 4.5-5.6) longer, respectively, compared to those with poor lifestyles. In contrast, the life expectancy gain for those without VHD was 4.4 years (95% CI, 4.0-4.8) for women and 5.3 years (95% CI, 4.8-5.7) for men when adhering to an ideal lifestyle versus a poor one. CONCLUSIONS: Adopting a healthier lifestyle can significantly slow down the progression from free of VHD to incident VHD and further to death and increase life expectancy for both individuals with and without VHD within diverse socioeconomic elderly populations.
Subject(s)
Heart Valve Diseases , Life Expectancy , Life Style , Humans , Female , Male , Aged , United Kingdom/epidemiology , Middle Aged , Heart Valve Diseases/epidemiology , Heart Valve Diseases/mortality , Disease Progression , Aged, 80 and over , Cohort Studies , Social ClassABSTRACT
Background: Valvular heart disease (VHD) represents a spectrum of cardiac conditions, including valvular stenosis, valvular regurgitation, or mixed lesions affecting single or multiple valves. The severity of VHD has emerged as a major cause of cardiovascular (CV) morbidity and mortality among the older population in the United States (U.S). Objective: To evaluate temporal trends in mortality associated with VHD in the elderly U.S population between 1999 and 2019. Methods: We utilized the CDC WONDER database for VHD mortality in adults ≥75 from 1999 to 2019, using ICD-10 codes. Age-adjusted mortality rates (AAMR) per 100,000 people with associated annual percentage change (APC) were calculated. Joinpoint regression was used to assess the overall trends and trends for demographic, geographic, and type of valvular disease subgroups. Results: A total of 666,765 VHD deaths in older adults from 1999 to 2019 was identified, with an initial decline in AAMR until 2007 with an APC: 0.62, 95 % CI (-1.66-0.33), stability until 2014, and a significant decrease until 2019 (APC: 1.47, 95 % CI [-2.24-1.04], P < 0.0001). Men consistently had higher AAMRs compared to women (overall AAMR men: 173.6; women: 138.2). The AAMRs were found to be highest in the White (166.5), followed by American Indian or Alaska Native population at (93.8) Hispanic or Latino at (80.7), Black or African American populations at (74.1) and lastly Asian or Pacific Islander (73.4). Non-metropolitan areas manifested higher AAMRs for deaths related to VHD than metropolitan areas (overall AAMRs 160.5 vs 149.5) respectively. State-wide AAMRs varied, with the highest in Vermont at 324.2 (95 % CI [313.0-335.4], P < 0.0001) and the lowest in Mississippi at 88.0 (95 % CI [85.0-91.0], P < 0.0001). Non-rheumatic and aortic valve disorders in adults ≥75 years had higher mortality rates compared to rheumatic or mitral valve conditions in those <75 years. Conclusion: Our study showed a decline in U.S. VHD mortality from 1999 to 2019 but found persistent disparities by gender, race, age, region, and VHD type. Targeted policies for prevention and early diagnosis are needed to address these inequalities.
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BACKGROUND: Atrial fibrillation (AF) poses a significant stroke risk in heart disease patients. This systematic review aims to evaluate the efficacy and safety of non-vitamin K oral antagonists (NOACs) versus vitamin K antagonists (VKAs) in AF patients with and without any valvular heart disease (VHD/N-VHD). METHODS: A systematic search was conducted on PubMed, Scopus, and Google Scholar up to March 3, 2022. Efficacy and safety parameters were analyzed. RESULTS: A total of 85,423 subjects from 10 studies were included in this meta-analysis. NOACs and VKAs showed similar effects on ischemic stroke in AF patients with VHD/N-VHD (RR 0.97; 95% CI 0.72-1.30; p = 0.83) and also on systemic embolic events (RR 1.02; 95% CI 0.83-1.25; p = 0.86). Similar effects were seen in VHD and N-VHD subgroups. Both treatments had similar effects on myocardial infarction in AF patients with VHD/N-VHD (RR 0.79; 95% CI 0.49-1.26; p = 0.32), VHD (RR 0.78; 95% CI 0.59-1.02; p = 0.07), and N-VHD subgroups (RR 0.82; 95% CI 0.30-2.21; p = 0.69). NOACs reduced the risk of intracranial bleeding in AF VHD/N-VHD (RR 0.64; 95% CI 0.54-0.77; p < 0.0001), VHD (RR 0.59; 95% CI 0.42-0.82; p = 0.002), and N-VHD subgroups (RR 0.70; 95% CI 0.57-0.85; p = 0.0003). Additionally, NOACs reduced the risk of gastrointestinal bleeding in AF VHD/N-VHD (RR 0.80; 95% CI 0.66-0.96; p = 0.02), specifically in the VHD subgroup (RR 0.69; 95% CI 0.54-0.89; p = 0.004). Moreover, NOACs were associated with a decreased risk for minor and non-fatal bleeding in AF patients with VHD/N-VHD (RR 0.86; 95% CI 0.75-0.99; p = 0.04). CONCLUSION: NOACs are effective and safe for ischemic stroke, systemic embolic events, myocardial infarction, intracranial bleeding, and gastrointestinal bleeding in AF patients with VHD/N-VHD.
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BACKGROUND: A prior Society of Thoracic Surgeons/American College of Cardiology TVT (Transcatheter Valve Therapy) Registry-based analysis reported similar 1-year clinical outcomes with small (20-mm) vs large (≥23-mm) balloon-expandable valves (BEV). OBJECTIVES: The aim of this study was to describe mid-term 3-year clinical outcomes for small vs large BEV and the relationship between discharge echocardiographic mean gradient (MG) and different definitions of prothesis-patient mismatch (PPM) with clinical outcomes. METHODS: Using the TVT Registry with Centers for Medicare and Medicaid Services linkage, a propensity-matched analysis of patients receiving 20- vs ≥23-mm BEVs was performed. Spline curves and Kaplan-Meier plots with adjusted HRs determined the relationship between MG and 3-year mortality. RESULTS: In total, 316,091 patients were analyzed; after propensity matching, 8,100 pairs of each group were compared. The 20-mm BEV was associated with higher MGs compared with ≥23-mm BEVs (16.2 ± 7.2 mm Hg vs 11.8 ± 5.7 mm Hg; P < 0.0001). At 3 years, there was no difference in mortality between 20- and ≥23-mm BEVs (31.5% vs 32.5%, respectively; HR: 0.97; 95% CI: 0.90-1.05). Compared with an MG of 10 to 30 mm Hg, an MG <10 mm Hg (HR: 1.25; 95% CI:1.22-1.27) was associated with increased 3-year mortality. Measured severe PPM and predicted no PPM were associated with increased 3-year mortality (33.5% vs 32.9% vs 32.1%; P < 0.0001) and (33.5% vs 31.1% vs 30%; P < 0.0001), respectively. Low MG and severe measured PPM were associated with lower left ventricular ejection fraction (LVEF). CONCLUSIONS: Patients with small-prosthesis BEVs (20 mm) had identical 3-year survival as those with larger (≥23-mm) BEV valves. Severe measured PPM and low MG (<10 mm Hg), but not predicted severe PPM, were associated with lower LVEF and increased mortality, suggesting that LVEF is the culprit for worse outcomes.
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A 54-year-old patient with a medical history of hypertension, dyslipidemia, and diabetes underwent mitral valve replacement surgery with a biologic valve. During a chest computed tomography scan for breast neoplasia staging, a reduced luminal filling in the left atrium (3.6 cm) was unexpectedly found, prompting further cardiac evaluation. The patient was referred to the emergency department experiencing shortness of breath and fatigue, which improved after furosemide administration, and remaining stable throughout hospitalization. A transesophageal echocardiogram was performed the following day and revealed a biologic mitral valve prosthesis slightly displaced toward the left ventricle with an average transprosthetic gradient of 7 mmHg. Notably, a sizable intermediate echogenic mass measuring 3.0 cm × 3.5 cm was detected and attached to the prosthesis ring in a lateral and posterior position, within the left atrium. A mild degree of periprosthetic regurgitation was also noted. Given the substantial suspicion that the observed mass was a thrombus, the patient was commenced on anticoagulation therapy while awaiting cardiac magnetic resonance imaging for better characterization of the mass. Over 4 weeks, the thrombus notably decreased in size, disappearing entirely by the 6th week. This case highlights the significance of employing multiple imaging techniques in managing cardiac masses. The incidental discovery of the mass, its characterization, and subsequent management through anticoagulation, followed by confirmation and monitoring through echocardiogram, underscore the importance of a multimodal approach in diagnosing and treating such conditions.
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There has been increasing evidence supporting the importance of left atrial (LA) functional analysis and measurement in various physiologic and pathologic cardiovascular conditions due to its high diagnostic and prognostic values. Assessment of LA strain (LAS) has emerged as an early marker of subclinical LA dysfunction. Using speckle-tracking echocardiography, LAS can be measured in all phases of LA function (reservoir, conduit, and booster pump). In valvular heart disease (VHD), surgical and nonsurgical interventions should be performed before irreversible left ventricular (LV) and/or LA myocardial dysfunction. The current guidelines recommended using LV strain as a parameter for early detection and timely intervention. Currently, many published data have shown the diagnostic and prognostic values of LAS in VHD, which is encouraging to integrate LAS during echo assessment. In this review, we aim to collect the current data about the clinical utility of LAS changes in risk stratification, predicting outcome, and guiding the time of intervention in VHD. The review summarized these data according to the type of valve pathologies.
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BACKGROUND: Aortic stenosis (AS) and mitral regurgitation (MR) result in different patterns of left ventricular remodeling and hypertrophy. OBJECTIVES: We characterized left ventricular wall stress (LVWS) profiles in pressure and volume-overloaded systems, examined the relationship between baseline LVWS and cardiac remodeling, and assessed the acute effects of valve intervention on LVWS using invasive pressures combined with cardiac magnetic resonance (CMR) imaging measures of left ventricular volumes/mass. METHODS: A total of 47 patients with severe AS undergoing transcatheter aortic valve replacement (TAVR) and 15 patients with severe MR undergoing MitraClip (MC) underwent a 6-minute walk test (6MWT), transthoracic echocardiogram, and CMR before their procedures. Catheters in the left ventricle were used to record hemodynamic changes before and after valve/clip deployment. This was integrated with CMR data to calculate LVWS before and after intervention. RESULTS: The TAVR group demonstrated significant reductions in systolic LVWS post procedure (median 24.7 Pa [IQR: 14 Pa] pre vs median 17.3 Pa [IQR: 12 Pa] post; P < 0.001). The MC group demonstrated significant reductions in diastolic LVWS (median 6.4 Pa [IQR: 5 Pa] pre vs median 4.3 Pa [IQR: 4.1 Pa] post; P = 0.021) with no significant change in systolic LVWS (30.6 ±1.61 pre vs 33 ±2.47 Pa post; P = 0.16). There was an inverse correlation between baseline systolic LVWS and 6MWT in the TAVR group (r = -0.31; P = 0.04). CONCLUSIONS: TAVR results in significant reductions in systolic LVWS acutely. MC results in significant reductions in diastolic LVWS. Higher baseline systolic LVWS in TAVR is associated with shorter 6MWT suggesting that in AS, LVWS may be a useful marker of early decompensation.
Subject(s)
Aortic Valve Stenosis , Mitral Valve Insufficiency , Transcatheter Aortic Valve Replacement , Ventricular Remodeling , Humans , Male , Female , Transcatheter Aortic Valve Replacement/methods , Aortic Valve Stenosis/surgery , Aortic Valve Stenosis/physiopathology , Aortic Valve Stenosis/diagnostic imaging , Aged , Ventricular Remodeling/physiology , Mitral Valve Insufficiency/surgery , Mitral Valve Insufficiency/physiopathology , Mitral Valve Insufficiency/diagnostic imaging , Aged, 80 and over , Magnetic Resonance Imaging, Cine/methods , Echocardiography , Heart Ventricles/diagnostic imaging , Heart Ventricles/physiopathologyABSTRACT
PURPOSE: This meta-analysis aimed to evaluate the efficacy and safety of non-vitamin K antagonist oral anticoagulants (NOACs) compared with vitamin K antagonists (VKAs) in patients with atrial fibrillation (AF) and type 2 valvular heart disease (VHD). METHODS: We searched the PubMed, LILACS, and MEDLINE databases to retrieve, randomized controlled trials (RCTs) comparing NOACs and VKAs in patients with AF and type 2 VHD, excluding mitral stenosis (moderate to severe, of rheumatic origin) or mechanical heart valves. The efficacy outcomes assessed were stroke and systemic embolism (SE), while safety outcomes included major bleeding and intracranial hemorrhage (ICH). RESULTS: Seven RCTs, including 16,070 patients with AF and type 2 VHD, were included. NOACs reduced the risk of stroke/SE (relative risk [RR], 0.75; 95% confidence interval [CI], 0.64-0.89; P = 0.0005), with no significant difference in major bleeding (RR, 0.88; 95% CI, 0.64-1.21; P = 0.43). The risk of ICH was reduced with NOACs (RR, 0.46; 95% CI, 0.27-0.77; P = 0.003). For patients with AF and bioprosthetic heart valve (five trials, 2805 patients), stroke/SE risks (RR, 0.65, 95% CI, 0.44-0.96) with NOACs were superior to VKAs. Major bleeding risks without ENVISAGE TAVI AF trial (RR, 0.53; 95% CI, 0.30-0.94; P = 0.03) with NOACs were superior to VKAs. The risks of ICH (RR, 0.61; 95% CI 0.34-1.09; P = 0.09) with NOACs were comparable to VKAs. CONCLUSIONS: NOACs demonstrate efficacy and safety in patients with AF and type 2 VHD and reduce the risk of stroke/SE and ICH when compared with those with VKAs.
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OBJECTIVE: The proximal isovelocity surface area (PISA) method is a well-established approach for mitral regurgitation (MR) quantification. However, it exhibits high inter-observer variability and inaccuracies in cases of non-hemispherical flow convergence and non-holosystolic MR. To address this, we present EasyPISA, a framework for automated integrated PISA measurements taken directly from 2-D color-Doppler sequences. METHODS: We trained convolutional neural networks (UNet/Attention UNet) on 1171 images from 196 recordings (54 patients) to detect and segment flow convergence zones in 2-D color-Doppler images. Different preprocessing schemes and model architectures were compared. Flow convergence surface areas were estimated, accounting for non-hemispherical convergence, and regurgitant volume (RVol) was computed by integrating the flow rate over time. EasyPISA was retrospectively applied to 26 MR patient examinations, comparing results with reference PISA RVol measurements, severity grades, and cMRI RVol measurements for 13 patients. RESULTS: The UNet trained on duplex images achieved the best results (precision: 0.63, recall: 0.95, dice: 0.58, flow rate error: 10.4 ml/s). Mitigation of false-positive segmentation on the atrial side of the mitral valve was achieved through integration with a mitral valve segmentation network. The intraclass correlation coefficient was 0.83 between EasyPISA and PISA, and 0.66 between EasyPISA and cMRI. Relative standard deviations were 46% and 53%, respectively. Receiver operator characteristics demonstrated a mean area under the curve between 0.90 and 0.97 for EasyPISA RVol estimates and reference severity grades. CONCLUSION: EasyPISA demonstrates promising results for fully automated integrated PISA measurements in MR, offering potential benefits in workload reduction and mitigating inter-observer variability in MR assessment.
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With echocardiography standing as the most widely used cardiac imaging modality, echocardiography report interpretation is a core responsibility of junior doctors. The literature, however, reveals a deficit in echocardiography education. The implications of this for patient care should not be ignored. To address this need, a hybrid teaching session was developed for junior (intern and resident grade) doctors, with the aim to increase understanding of echocardiography and increase confidence in report interpretation. Pre- and post-session data were analysed. Results revealed that the vast majority of respondents received less than an hour of echocardiography teaching at medical school, with over two-thirds receiving less than an hour in the postgraduate setting. A total of 80% of doctors interpreted echocardiography reports weekly, with almost all doctors perceiving this skill as important. Despite this, an overwhelming majority of doctors did not feel confident interpreting reports. The educational intervention achieved significant increases in perceived understanding of echocardiography and confidence with report interpretation. Participants were better able to identify cardiac pathology and understand report terminology. This intervention has the scope to improve patient safety through better management of cardiac patients and recognition of pathology from echocardiography. This work also identifies a need for more echocardiography education, having uncovered a concerning lack of confidence amongst junior doctors and an appetite for further teaching on this important topic.
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The global prevalence of obesity has more than doubled over the past four decades, currently affecting more than a billion individuals. Beyond its recognition as a high-risk condition that is causally linked to many chronic illnesses, obesity has been declared a disease per se that results in impaired quality of life and reduced life expectancy. Notably, two-thirds of obesity-related excess mortality is attributable to cardiovascular disease. Despite the increasingly appreciated link between obesity and a broad range of cardiovascular disease manifestations including atherosclerotic disease, heart failure, thromboembolic disease, arrhythmias, and sudden cardiac death, obesity has been underrecognized and sub-optimally addressed compared with other modifiable cardiovascular risk factors. In the view of major repercussions of the obesity epidemic on public health, attention has focused on population-based and personalized approaches to prevent excess weight gain and maintain a healthy body weight from early childhood and throughout adult life, as well as on comprehensive weight loss interventions for persons with established obesity. This clinical consensus statement by the European Society of Cardiology discusses current evidence on the epidemiology and aetiology of obesity; the interplay between obesity, cardiovascular risk factors and cardiac conditions; the clinical management of patients with cardiac disease and obesity; and weight loss strategies including lifestyle changes, interventional procedures, and anti-obesity medications with particular focus on their impact on cardiometabolic risk and cardiac outcomes. The document aims to raise awareness on obesity as a major risk factor and provide guidance for implementing evidence-based practices for its prevention and optimal management within the context of primary and secondary cardiovascular disease prevention.
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The global prevalence of obesity has more than doubled over the past four decades, currently affecting more than a billion individuals. Beyond its recognition as a high-risk condition that is causally linked to many chronic illnesses, obesity has been declared a disease per se that results in impaired quality of life and reduced life expectancy. Notably, two-thirds of obesity-related excess mortality is attributable to cardiovascular disease. Despite the increasingly appreciated link between obesity and a broad range of cardiovascular disease manifestations including atherosclerotic disease, heart failure, thromboembolic disease, arrhythmias, and sudden cardiac death, obesity has been underrecognized and sub-optimally addressed compared with other modifiable cardiovascular risk factors. In the view of major repercussions of the obesity epidemic on public health, attention has focused on population-based and personalized approaches to prevent excess weight gain and maintain a healthy body weight from early childhood and throughout adult life, as well as on comprehensive weight loss interventions for persons with established obesity. This clinical consensus statement by the European Society of Cardiology discusses current evidence on the epidemiology and aetiology of obesity; the interplay between obesity, cardiovascular risk factors and cardiac conditions; the clinical management of patients with cardiac disease and obesity; and weight loss strategies including lifestyle changes, interventional procedures, and anti-obesity medications with particular focus on their impact on cardiometabolic risk and cardiac outcomes. The document aims to raise awareness on obesity as a major risk factor and provide guidance for implementing evidence-based practices for its prevention and optimal management within the context of primary and secondary cardiovascular disease prevention.
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Non-bacterial thrombotic endocarditis (NBTE) is a form of non-infective endocarditis characterized by the deposition of sterile fibrin and platelets on cardiac valves. Even though some studies have identified important pathophysiological features, many aspects remain poorly understood. Given its wide availability, transthoracic echocardiography is typically the initial diagnostic approach to the patient. Additionally, recent technological advancements in transesophageal echocardiography, such as three-dimensional and multiplanar reconstruction analysis, have significantly improved diagnostic accuracy over time. By presenting our case series and performing a literature review, we focused on the main pathophysiologic, diagnostic, and therapeutic aspects of this rare but potentially life-threatening disease.
Subject(s)
Heart Valve Diseases , Humans , Treatment Outcome , Heart Valve Diseases/diagnostic imaging , Heart Valve Diseases/physiopathology , Heart Valve Diseases/surgery , Heart Valve Diseases/therapy , Heart Valve Prosthesis Implantation/instrumentation , Heart Valve Prosthesis Implantation/adverse effects , Risk Factors , Clinical Decision-MakingABSTRACT
BACKGROUND AND AIMS: To assess sex differences in disease characteristics and treatment of patients with severe native valvular heart disease (VHD) included in the VHD II EURObservational Research Programme. METHODS: A total of 5219 patients were enrolled in 208 European and North African centres and followed for 6 months [41.2% aortic stenosis (AS), 5.3% aortic regurgitation (AR), 4.5% mitral stenosis (MS), 21.3% mitral regurgitation (MR), 2.7% isolated right-sided VHD, 24.9% multiple left-sided VHD]. Indications for intervention were considered concordant if corresponding to class I recommendations specified in the 2012 ESC or 2014 AHA/ACC VHD guidelines. RESULTS: Overall, women were older, more symptomatic, and presented with a higher EuroSCORE II. Bicuspid aortic valve and AR were more prevalent among men while mitral disease, concomitant tricuspid regurgitation (TR), and AS above age 65 were more prevalent among women. On multivariable regression analysis, concordance with recommended treatment was significantly poorer in women with MS and primary MR (both P < .001). Age, patient refusal, and decline of symptoms after conservative treatment were reported significantly more often as reasons to withhold the intervention in females. Concomitant tricuspid intervention was performed at a similar rate in both sexes although prevalence of significant TR was significantly higher in women. In-hospital and 6-month survival did not differ between sexes. CONCLUSIONS: (i) Valvular heart disease subtype varied between sexes; (ii) concordance with recommended intervention for MS and primary MR was significantly lower for women; and (iii) survival of men and women was similar at 6 months.
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Background: We aimed to assess the characteristics, management and long-term prognosis of a cohort of patients with multiple valvular disease, focusing on the context of severe mitral or aortic disease with concomitant significant tricuspid regurgitation (TR). Methods: After using a propensity score matching for age, 975 patients with ≥ moderate TR, diagnosed at our centers from 2012 to 2020, were included and divided in four groups, including isolated TR patients as reference group. Primary endpoint was all-cause death (ACD), secondary endpoint was the composite of heart failure (HF) hospitalization + any valvular intervention. Results: Patients with isolated TR (356, 37 %) had more history of atrial fibrillation and were more often asymptomatic and with preserved left-ventricular ejection fraction (LVEF). Patients with severe mitral regurgitation (MR) + TR (466, 48 %) showed higher rates of concomitant coronary artery disease, advanced functional class symptoms and larger left atrial volumes. Severe aortic stenosis (AS) patients (131, 13 %) were older, with more comorbidities and lower LVEF. Patients with severe aortic regurgitation and TR (22, 2 %) were younger, with larger LV dimensions and higher pulmonary arterial pressures.After a median follow-up of 2.8 years, both endpoints were univariably more frequent in patients with severe AS + TR (all p < 0.001), but after comprehensive adjustment difference in the primary endpoint became insignificant, underscoring the serious outcomes of all significant TR groups significantly. Overall, in 44 (5 %) patients tricuspid intervention was performed, with no differences between groups in term of frequency of concomitant or staged tricuspid valve surgical treatment. Conclusions: In the context of severe left-sided VD, concomitant significant TR is common, and each subtype presents with different clinical and echocardiographic features: patients with severe AS and TR have considerable worse prognosis, although comprehensive adjustment reflected the poor outcomes affecting all types of patients with significant TR. In this scenario, TR was profoundly undertreated.