Search Results (45)

Background: Sodium–glucose cotransporter 2 inhibitors (SGLT2 inhibitors), initially developed for glycemic control in type 2 diabetes, have demonstrated robust cardiovascular and renal benefits. Emerging evidence suggests that these agents may also affect valvular pathobiology, particularly in degenerative aortic stenosis (AS), through anti-inflammatory and antifibrotic mechanisms. Objectives: This study evaluated whether SGLT2 inhibitor use is associated with improved clinical outcomes in degenerative AS, including all-cause mortality and the need for SAVR or TAVR, recognizing that these endpoints represent surrogate rather than direct measures of valve hemodynamic progression. Methods: A retrospective cohort analysis was conducted using TriNetX, a federated electronic medical record-based research network. Diagnoses are captured using ICD-9/ICD-10-CM codes and medications using ATC codes. Adults with non-rheumatic AS were stratified by SGLT2 inhibitors use. Propensity score matching (1:1) was performed to balance baseline characteristics between treated and untreated groups (n = 10,912 per group). Primary outcomes included all-cause mortality, TAVR, and SAVR during follow-up. Echocardiographic parameters (AVA, Vmax, mean gradient) were not systematically available. Results: After adjustment for comorbidities, SGLT2 inhibitor use was independently associated with lower all-cause mortality (6.15% vs. 9.34% HR 0.595; 95% CI 0.552–0.641; p < 0.001), TAVR (2.81% vs. 2.89% HR 0.835; 95% CI 0.746–0.934; p = 0.002), SAVR (1.28% vs. 1.90% HR 0.514; 95% CI 0.442–0.599; p < 0.001), cardiac arrest (0.82% vs. 1.21% HR 0.71; 95% CI 0.582–0.867; p < 0.001), and end-stage kidney disease (0.40% vs. 1.0% HR 0.292; 95% CI 0.222–0.384; p < 0.001). Although these associations may suggest slower disease progression, interpretation is limited by the lack of systematic echocardiographic follow-up. Conclusions: In addition to their established benefits in heart failure and renal protection, SGLT2 inhibitors may have valve-preserving effects in degenerative AS. Because true hemodynamic progression could not be evaluated, these results should be viewed as associations with surrogate clinical endpoints. Prospective studies with standardized imaging are required to determine whether SGLT2 inhibition can directly alter the course of this currently untreatable disease Full article

Rheumatic heart disease (RHD) remains a major cause of preventable morbidity in low- and middle-income countries. As the most serious sequel of acute rheumatic fever (ARF) caused by Streptococcus pyogenes, RHD arises from molecular mimicry that drives autoimmune damage of cardiac valves. We systematically reviewed human studies (1977–2025) following PRISMA to clarify systemic immune signatures associated with valvular pathology. Searches of PubMed, LILACS, ScienceDirect, and Web of Science found 29 studies: 22 RHD and 7 ARF. In ARF, elevations in IL-6, IL-8, IL-17F, GM-CSF, TNF-a, and CXCL10 occurred alongside increased activity of CD4⁺ Th1 and MAIT cells. In RHD, a consistent inflammatory–fibrotic profile emerged with raised IL-17, IFN-γ, TNF-a, TGF-β1, Tenascin-C, and prothymosin alpha (ProTα) in blood and valve tissue. CD4⁺ and CD8⁺ T cells were implicated in valve injury; ProTα correlated with cytotoxic activity of circulating CD8⁺ T cells. Several mediators (IL-6, TNF-a, IL-8, CXCL10, CCL2, CCL19) were identified in RHD studies as being associated with inflammation, cell recruitment, and clinical severity. Systemic dysregulation mirrored local valve inflammation, suggesting circulating molecules may index ongoing cardiac damage. These findings underscore a central role for T cells and pro-inflammatory cytokines in RHD and highlight candidate prognostic markers and therapeutic targets to inform translational studies and trials. Full article

Background/Objectives: Giant atrial chambers are rare but clinically important conditions, most often linked to rheumatic mitral valve disease, though they may also occur in congenital or other acquired disorders. Despite their low prevalence, they entail major hemodynamic, arrhythmogenic, and extracardiac risks. This study aimed to review recent evidence on giant atrial pathology—including giant left atrium (GLA), giant right atrium (GRA), and atrial appendage aneurysms—and to illustrate its relevance through cases of symptomatic extracardiac compression. Methods: A PubMed search on 15 September 2025 using “giant atrium” and limited to human, free full-text studies from the last 10 years yielded 93 results. After screening, 21 reports describing 24 cases were analyzed and compared with institutional experience. Results: GLA is most often defined by an anteroposterior diameter ≥6.5 cm or ≥8 cm, while criteria for GRA and appendage aneurysms remain inconsistent. Reported complications include atrial fibrillation, thromboembolism, and compression of mediastinal structures, with presentations such as dysphagia or airway obstruction. While valve surgery alone may suffice, many authors recommend concomitant atrial reduction or aneurysm resection in symptomatic patients. Conclusions: Giant atrial pathology, though uncommon, carries significant cardiac and extracardiac implications. Management should be individualized, and awareness of atypical manifestations is critical for timely diagnosis and treatment. Full article

Primary tricuspid regurgitation (TR) is an underrecognized valve disease characterized by structural abnormalities of the tricuspid valve (TV) apparatus, including leaflet prolapse, flail, rheumatic degeneration, carcinoid involvement and congenital malformations such as Ebstein’s anomaly. Historically neglected and often misclassified as functional, primary TR has recently gained attention due to advances in multimodality imaging and increased awareness of its pathophysiological complexity and adverse outcomes. A major challenge that remains is the accurate diagnosis of primary TR, as well as the optimal timing for intervention, particularly in asymptomatic patients. While surgical repair or replacement has been the traditional approach, recent developments in transcatheter therapies, such as tricuspid edge-to-edge repair, have broadened the therapeutic landscape for patients considered at high surgical risk. In this context, personalized medicine has emerged as a central paradigm in the management of this valvular disease. Tailored therapeutic decisions should include anatomical, functional, and clinical parameters, as well as patient-specific risk factors such as age and comorbidities. Advanced imaging modalities, including 3D echocardiography and cardiac magnetic resonance, are essential for guiding this individualized approach. This review summarizes the current understanding of the etiology, pathophysiology, diagnostic tools, and treatment strategies for primary TR, highlighting the critical role of personalized treatment pathways in optimizing clinical outcomes. Full article

(1) Background: Concomitant mild aortic valve disease is frequently found in patients undergoing rheumatic mitral valve surgery. To date, only a limited number of single-center studies have specifically addressed the untreated baseline aortic valve disease long-term progression and reoperation rate. Thus, we conducted a meta and landmark analysis to systematically review the issue. (2) Methods: This study investigated the long-term prognostic of baseline mild aortic valve disease in patients undergoing rheumatic mitral valve surgery, based on evidence from PubMed, Embase, Cochrane Library, and Web of Science databases. (3) Results: Meta analysis revealed that patients with mild aortic valve disease had a higher risk of disease progression, with a 3.3-fold risk in the 0–5-year follow-up, which jumped to a hazard ratio of 6.42 in longer-term follow-up (5–25 years). Patients with aortic stenosis had an 8.37-fold risk of progression compared with aortic regurgitation and appeared to be poorly related to the time cut-off. Similarly, higher reoperation rates at long-term follow-up were seen in aortic stenosis patients. (4) Conclusions: This study suggests that patients with mild aortic valve disease at baseline have poorer long-term aortic valve-related progression and reoperation rates, especially aortic stenosis. For those with concomitant aortic stenosis, further investigation of the impact of lesion progression is warranted. Full article

Background: Sodium–glucose cotransporter 2 inhibitors (SGLT2i) have shown cardioprotective effects beyond glucose control. In aortic stenosis, SGLT2 expression is upregulated in myocardium and valve tissue, contributing to inflammation, oxidative stress, thrombogenicity, and calcification. SGLT2 inhibition may counteract these mechanisms, potentially reducing bioprosthetic valve failure after transcatheter aortic valve replacement (TAVR), where the diseased native valve remains in place. Objectives: This study aimed to evaluate whether SGLT2i use is associated with improved clinical outcomes, including all-cause mortality and bioprosthetic valve failure, following TAVR. Methods: We conducted a retrospective cohort study using the TriNetX global health research network. Adults with non-rheumatic aortic stenosis who underwent TAVR were stratified by SGLT2i use. Propensity score matching (1:1) was applied to balance baseline characteristics (n = 2297 per group). Primary outcomes were all-cause mortality and bioprosthetic valve failure during follow-up. Results: Before matching, SGLT2i users had more cardiovascular comorbidities. After matching, SGLT2i use was associated with a significantly lower risk of all-cause mortality (HR: 0.83; 95% CI: 0.71–0.97; p = 0.02) and bioprosthetic valve failure (HR: 0.62; 95% CI: 0.39–0.99; p = 0.04). Conclusions: In a large real-world cohort of TAVR recipients, SGLT2i use was independently associated with reduced mortality and lower risk of bioprosthetic valve failure. These findings support a potential disease-modifying role for SGLT2 inhibitors in this high-risk population and warrant further prospective investigation. Full article

Although most commonly diagnosed in the elderly population, aortic stenosis can affect younger patients, being the most frequent valvular disease requiring replacement interventions, either through surgical procedures (SAVR = surgical aortic valve replacement) or through transcatheter aortic valve implantation (TAVI). In young patients, aortic stenosis generally occurs due to congenital malformations, such as bicuspid aortic valves (BAVs), or to rheumatic valve disease, both of which present specific anatomical characteristics. There is an upward trend among young patients regarding TAVI, due to the possibility of avoiding the complications of open-heart surgery while offering a faster recovery, although it is important to note that complications, such as conduction disturbances, paravalvular leaks (PVL), or strokes, can arise. Because of the current lack of long-term data, the implications of these complications among young patients are not well established. Moreover, an important issue among young patients is the durability of the prosthesis, as patient survival is expected to exceed the device’s lifespan. The purpose of this review is to assess the current data on the most common causes of aortic stenosis and outcomes of TAVI in young patients, focusing on subgroups of patients with bicuspid aortic stenosis or rheumatic aortic stenosis, while emphasizing the potential complications, the durability of the aortic prosthesis, and reintervention possibilities. Full article

Background: Studies analyzing factors associated with mortality after intracranial stenting are limited. We aimed to investigate potential factors associated with 1-year mortality after urgent or elective intracranial stenting in those patients with intracranial atherosclerotic stenosis. Methods: Patients, who underwent urgent intracranial stenting of the target lesion either due to acute stroke unresponsive to mechanical thrombectomy, or who underwent elective stenting for symptomatic intracranial atherosclerotic stenosis were included in the study. The Modified Rankin Scale (mRS) score was evaluated on admission and grouped accordingly: ≤2 vs. >2. Restenosis and mortality rates in the 1-year follow-up were also analyzed. Results: A total of 60 patients were included in the study; the mean age was 60.2 (±10.8). The ratio of urgent/elective intracranial stenting was 7/53. Complete revascularization was achieved in all patients, but no periprocedural complications occurred. The rate of in-hospital mortality was 1/60, 1-year mortality due to any cause 4/60, and restenosis in a 1-year follow-up was 4/60. The age over 65 years, previous history of stroke, atrial fibrillation (AF), and rheumatic mitral valve disease were associated with mortality (p < 0.001, p = 0.002, p = 0.017, and p = 0.003, respectively). The median mRS score on admission was lower in the surviving patients at 1 year (p = 0.001). Conclusions: Intracranial stenting may provide long-term survival with low adverse event rates in elective and selected emergency cases. Advanced age, poor functional status, previous stroke, AF, and rheumatic mitral valve disease are associated with 1-year mortality. Full article

Atrial fibrillation (AF) is a common arrhythmia in clinical practice, and oral anticoagulation is the cornerstone of stroke prevention in AF. Direct oral anticoagulants (DOAC) significantly reduce the incidence of intracerebral hemorrhage with preserved efficacy for preventing stroke compared to vitamin K antagonists (VKA). However, the pivotal randomized controlled trials (RCTs) of DOAC excluded patients with valvular heart disease, especially mitral stenosis, which remains an exclusion criterion for DOAC use. The INVICTUS study was a large multicenter global RCT aimed at evaluating the role of DOAC compared to VKA in stroke prevention among patients with rheumatic valvular AF. In this study, rivaroxaban failed to prove superiority over VKA in preventing the composite primary efficacy endpoints of stroke, systemic embolism, myocardial infarction, and death. Unfortunately, the bleeding rates were not lower with rivaroxaban either. The death and drug discontinuation rates were higher in the DOAC arm. Close to the heels of the dismal results of INVICTUS, an apixaban trial in prosthetic heart valves, PROACT-Xa, was also prematurely terminated due to futility. Hence, for AF complicating moderate-to-severe mitral stenosis or prosthetic valve VKA remains the standard of care. However, DOAC can be used in patients with surgical bioprosthetic valve implantation, TAVR, and other native valve diseases with AF, except for moderate-to-severe mitral stenosis. Factor XI inhibitors represent a breakthrough in anticoagulation as they aim to dissociate thrombosis from hemostasis, thereby indicating a potential to cut down bleeding further. Multiple agents (monoclonal antibodies—e.g., osocimab, anti-sense oligonucleotides—e.g., fesomersen, and small molecule inhibitors—e.g., milvexian) have garnered positive data from phase II studies, and many have entered the phase III studies in AF/Venous thromboembolism. Future studies on conventional DOAC and new-generation DOAC will shed further light on whether DOAC can dethrone VKA in valvular heart disease. Full article

Background/Objectives: We assessed the effectiveness and safety of vitamin K antagonists (VKAs) versus direct oral anticoagulants (DOACs) in patients with atrial fibrillation (AF) using artificial intelligence techniques. Methods: This is a retrospective study in 15 Spanish hospitals (2014–2020), including adult AF patients with no history of anticoagulation, thrombosis events, rheumatic mitral valvular heart disease, mitral valve stenosis, or pregnancy. We employed EHRead^® technology based on natural language processing (NLP) and machine learning (ML), along with SNOMED-CT terminology, to extract clinical data from electronic health records (EHRs). Using propensity score matching (PSM), the effectiveness, safety, and hospital mortality of VKAs versus DOACs were analyzed through Kaplan–Meier curves and Cox regression. Results: Out of 138,773,332 EHRs from 4.6 million individuals evaluated, 44,292 patients were included, 79.6% on VKAs and 20.4% on DOACs. Most patients were elderly [VKA 78 (70, 84) and DOAC 75 (66, 83) years], with numerous comorbidities (75.5% and 70.2% hypertension, 47.2% and 39.9% diabetes, and 40.3% and 34.8% heart failure, respectively). Additionally, 60.4% of VKA and 48.7% of DOAC users had a CHA2DS2-VASc Score ≥4. After PSM, 8929 patients per subgroup were selected. DOAC users showed a lower risk of thrombotic events [HR 0.81 (95% CI 0.70–0.94)], minor bleeding [HR 0.89 (95% CI 0.83–0.96)], and mortality [HR 0.80 (95% CI 0.69–0.92)]. Conclusions: Applying NLP and ML, we generated valuable real-world evidence on anticoagulated AF patients in Spain. Even in complex populations, DOACs have demonstrated a better safety and effectiveness profile than VKAs. Full article

Background/Objectives: Non-vitamin K antagonist oral anticoagulants (NOACs) have demonstrated similar effectiveness and safety profiles to vitamin K antagonists (VKAs) in treating nonvalvular atrial fibrillation (AF). Given their favorable pharmacological profile, including the rapid onset and offset of action, fixed dosing, and predictable pharmacokinetics with a consistent dose-response relationship, reducing the need for frequent blood tests, researchers have investigated the potential of NOACs in patients with AF and valvular heart disease (VHD). Methods: Clinical trials, excluding patients with mechanical prosthetic valves or moderate/severe mitral stenosis, have shown the benefits of NOACs over VKAs in this population. However, there is a need for further research to determine if these findings apply to mechanical valve prostheses and NOACs. Results: Several ongoing randomized controlled trials are underway to provide more definitive evidence regarding NOAC treatment in moderate to severe rheumatic mitral stenosis. Importantly, recent trials that included patients with atrial fibrillation and bioprosthetic valves (also transcatheter heart valves) have provided evidence supporting the safety of NOACs in this specific patient population. Ongoing research aims to clearly define the specific scenarios where NOACs can be safely and effectively prescribed for various types of VHD, including moderate/severe mitral stenosis and mechanical valves. Conclusions: The aim of this review is to accurately identify the specific situations in which NOACs can be prescribed in patients with VHD, with a focus centered on each type of valvulopathy. Full article

Background/Objectives: Aortic valve stenosis (AS) represents one of the most common valve diseases in the western world. It often leads to severe symptoms that can lead to a restriction of everyday life and thus to psychological stress. Therefore, we aimed to investigate the association between AS and depression in outpatients in Germany. Methods: The IQVIA^TM Disease Analyzer database was used to identify 14,681 individuals with non-rheumatic AS (ICD-10: I35.0 or I35.2). They were propensity score matched (1:1) based on age, sex, average yearly consultation frequency during the follow-up, and co-diagnoses to 14,681 patients without AS. Cox regression models were used to analyze the association between aortic stenosis and depression. Results: Within the follow-up period of up to 10 years, depression was diagnosed in 20.6% of AS patients compared to 20.0% in the matched cohort (p = 0.351). In the regression analysis, we were not able to discover an association between AS and a subsequent diagnosis of depression (HR: 1.03; 95% CI: 0.96–1.11). This effect was consistent among different age and sex groups. Conclusions: In the broad population of patients treated outside of hospital settings in Germany, AS was not associated with a higher incidence of depression. Full article

Rheumatic heart disease (RHD) caused by group A streptococcus infection is one of the most important reasons of cardiovascular morbidity and mortality in low- and middle-income countries. Aberrant host immune response modulated by polymorphisms in inflammatory response genes plays an important role in RHD pathogenesis. This study aimed to determine risk-associated polymorphic variants in inflammatory response genes in Caucasian RHD patients. A total of 251 Caucasian RHD patients and 300 healthy donors were recruited for this study, and 27 polymorphic sites in 12 genes (TLR1, TLR2, TLR4, TLR6, IL1B, IL6R, IL6, IL10, IL12RB1, IL12B, TNF and CRP) were analyzed using allele-specific PCR. It was demonstrated that the polymorphic variants rs1800871 and rs1800872 in the IL10 gene, rs 1130864, rs3093077 and rs1205 in the CRP gene, rs375947 in the IL12RB1 gene, rs 5743551 and rs5743611 in the TLR1 gene, and rs3775073 in the TLR6 gene can modify RHD risk in a gender- and age-dependent manner. The obtained results can be used to determine the personalized risk of RHD in healthy donors during medical examination or screening, as well as to develop appropriate early prevention strategies targeting RHD in the risk groups. Full article