Atorvastatin Effect on Aortic Dilatation and Valvular Calcification Progression in Bicuspid Aortic Valve (BICATOR): A Randomized Clinical Trial.

BACKGROUND: Ascending aorta dilation and aortic valve degeneration are common complications in patients with bicuspid aortic valve. Several retrospective studies have suggested the benefit of statins in reducing these complications. This study aimed to determine whether atorvastatin treatment is effective in reducing the growth of aortic diameters in bicuspid aortic valve and if it slows the progression of valve calcification. METHODS: In a randomized clinical trial, 220 patients with bicuspid aortic valve (43 women; 46±13 years of age) were included and treated with either 20 mg of atorvastatin per day or placebo for 3 years. Inclusion criteria were ≥18 years of age, nonsevere valvular dysfunction, nonsevere valve calcification, and ascending aorta diameter ≤50 mm. Computed tomography and echocardiography studies were performed at baseline and after 3 years of treatment. RESULTS: During follow-up, 28 patients (12.7%) discontinued medical treatment (15 on atorvastatin and 13 taking placebo). Thus, 192 patients completed the 36 months of treatment. Low-density lipoprotein cholesterol levels decreased significantly in the atorvastatin group (median [interquartile range], -30 mg/dL [-51.65 to -1.75 mg/dL] versus 6 mg/dL [-4, 22.5 mg/dL]; P<0.001). The maximum ascending aorta diameter increased with no differences between groups: 0.65 mm (95% CI, 0.45-0.85) in the atorvastatin group and 0.74 mm (95% CI, 0.45-1.04) in the placebo group (P=0.613). Similarly, no significant differences were found for the progression of the aortic valve calcium score (P=0.167) or valvular dysfunction. CONCLUSIONS: Among patients with bicuspid aortic valve without severe valvular dysfunction, atorvastatin treatment was not effective in reducing the progression of ascending aorta dilation and aortic valve calcification during 3 years of treatment despite a significant reduction in low-density lipoprotein cholesterol levels. REGISTRATION: URL: https://www.clinicaltrialsregister.eu; Unique identifier: 2015-001808-57. URL: https://www.clinicaltrials.gov; Unique identifier: NCT02679261.

Unraveling the Mechanisms of Valvular Heart Disease to Identify Medical Therapy Targets: A Scientific Statement From the American Heart Association.

Valvular heart disease is a common cause of morbidity and mortality worldwide and has no effective medical therapy. Severe disease is managed with valve replacement procedures, which entail high health care-related costs and postprocedural morbidity and mortality. Robust ongoing research programs have elucidated many important molecular pathways contributing to primary valvular heart disease. However, there remain several key challenges inherent in translating research on valvular heart disease to viable molecular targets that can progress through the clinical trials pathway and effectively prevent or modify the course of these common conditions. In this scientific statement, we review the basic cellular structures of the human heart valves and discuss how these structures change in primary valvular heart disease. We focus on the most common primary valvular heart diseases, including calcific aortic stenosis, bicuspid aortic valves, mitral valve prolapse, and rheumatic heart disease, and outline the fundamental molecular discoveries contributing to each. We further outline potential therapeutic molecular targets for primary valvular heart disease and discuss key knowledge gaps that might serve as future research priorities.

Valvular Heart Disease: New Concepts in Pathophysiology and Therapeutic Approaches.

This review discusses recent advancements in the field of valvular heart disease. Topics covered include recognition of the impact of atrial fibrillation on development and assessment of valvular disease, strategies for global prevention of rheumatic heart disease, understanding and management of secondary mitral regurgitation, the updated classification of bicuspid aortic valve disease, recognition of heightened cardiovascular risk associated with moderate aortic stenosis, and a growing armamentarium of transcatheter therapies.

BFGF attenuates aortic valvular interstitial cell calcification by inhibiting endoplasmic reticulum stress-mediated apoptosis.

The potential protective effect of basic fibroblast growth factor (BFGF) on the cardiovascular system has been proposed previously, however, its effect on calcific aortic valve disease (CAVD) and underlying mechanisms have not been elucidated. The valvular interstitial cell (VIC) were isolated from porcine aortic valve leaflets. To investigate the effect of BFGF on osteogenic differentiation of VIC, the osteogenic induced medium (OIM) and BFGF were added. The protein expression level was detected by Western blot, and apoptosis was determined by flow cytometry. The effect of BFGF on CAVD process in vivo was assessed by a rat CAVD model, which was identified by echocardiography and Alizarin red staining. The expression level of BFGF in the aortic valve and serum were significantly upregulated in CAVD patients compared to control group. In addition, exogenous BFGF injection attenuates CAVD process in vivo. The protein markers of osteogenic differentiation, endoplasmic reticulum stress (ERS), and apoptosis were significantly upregulated by culture with OIM. On the contrary, the aforementioned proteins were suppressed after adding 100 ng/mL of BFGF. Inhibition of PI3K/Akt and ERK1/2 pathways by specific inhibitors abolished the protective effect of BFGF. In conclusion, BFGF could alleviate the VIC calcification by inhibiting ERS-mediated apoptosis, which is partly regulated by activation of the PI3K/Akt and ERK1/2 signaling pathways. BFGF may provide a potential avenue for CAVD therapy.

Familial Associations of Prevalence and Cause-Specific Mortality for Thoracic Aortic Disease and Bicuspid Aortic Valve in a Large-Population Database.

BACKGROUND: Thoracic aortic disease and bicuspid aortic valve (BAV) likely have a heritable component, but large population-based studies are lacking. This study characterizes familial associations of thoracic aortic disease and BAV, as well as cardiovascular and aortic-specific mortality, among relatives of these individuals in a large-population database. METHODS: In this observational case-control study of the Utah Population Database, we identified probands with a diagnosis of BAV, thoracic aortic aneurysm, or thoracic aortic dissection. Age- and sex-matched controls (10:1 ratio) were identified for each proband. First-degree relatives, second-degree relatives, and first cousins of probands and controls were identified through linked genealogical information. Cox proportional hazard models were used to quantify the familial associations for each diagnosis. We used a competing-risk model to determine the risk of cardiovascular-specific and aortic-specific mortality for relatives of probands. RESULTS: The study population included 3 812 588 unique individuals. Familial hazard risk of a concordant diagnosis was elevated in the following populations compared with controls: first-degree relatives of patients with BAV (hazard ratio [HR], 6.88 [95% CI, 5.62-8.43]); first-degree relatives of patients with thoracic aortic aneurysm (HR, 5.09 [95% CI, 3.80-6.82]); and first-degree relatives of patients with thoracic aortic dissection (HR, 4.15 [95% CI, 3.25-5.31]). In addition, the risk of aortic dissection was higher in first-degree relatives of patients with BAV (HR, 3.63 [95% CI, 2.68-4.91]) and in first-degree relatives of patients with thoracic aneurysm (HR, 3.89 [95% CI, 2.93-5.18]) compared with controls. Dissection risk was highest in first-degree relatives of patients who carried a diagnosis of both BAV and aneurysm (HR, 6.13 [95% CI, 2.82-13.33]). First-degree relatives of patients with BAV, thoracic aneurysm, or aortic dissection had a higher risk of aortic-specific mortality (HR, 2.83 [95% CI, 2.44-3.29]) compared with controls. CONCLUSIONS: Our results indicate that BAV and thoracic aortic disease carry a significant familial association for concordant disease and aortic dissection. The pattern of familiality is consistent with a genetic cause of disease. Furthermore, we observed higher risk of aortic-specific mortality in relatives of individuals with these diagnoses. This study provides supportive evidence for screening in relatives of patients with BAV, thoracic aneurysm, or dissection.

Toll-Like Receptor 3 Mediates Aortic Stenosis Through a Conserved Mechanism of Calcification.

BACKGROUND: Calcific aortic valve disease (CAVD) is characterized by a phenotypic switch of valvular interstitial cells to bone-forming cells. Toll-like receptors (TLRs) are evolutionarily conserved pattern recognition receptors at the interface between innate immunity and tissue repair. Type I interferons (IFNs) are not only crucial for an adequate antiviral response but also implicated in bone formation. We hypothesized that the accumulation of endogenous TLR3 ligands in the valvular leaflets may promote the generation of osteoblast-like cells through enhanced type I IFN signaling. METHODS: Human valvular interstitial cells isolated from aortic valves were challenged with mechanical strain or synthetic TLR3 agonists and analyzed for bone formation, gene expression profiles, and IFN signaling pathways. Different inhibitors were used to delineate the engaged signaling pathways. Moreover, we screened a variety of potential lipids and proteoglycans known to accumulate in CAVD lesions as potential TLR3 ligands. Ligand-receptor interactions were characterized by in silico modeling and verified through immunoprecipitation experiments. Biglycan (Bgn), Tlr3, and IFN-α/ß receptor alpha chain (Ifnar1)-deficient mice and a specific zebrafish model were used to study the implication of the biglycan (BGN)-TLR3-IFN axis in both CAVD and bone formation in vivo. Two large-scale cohorts (GERA [Genetic Epidemiology Research on Adult Health and Aging], n=55 192 with 3469 aortic stenosis cases; UK Biobank, n=257 231 with 2213 aortic stenosis cases) were examined for genetic variation at genes implicated in BGN-TLR3-IFN signaling associating with CAVD in humans. RESULTS: Here, we identify TLR3 as a central molecular regulator of calcification in valvular interstitial cells and unravel BGN as a new endogenous agonist of TLR3. Posttranslational BGN maturation by xylosyltransferase 1 (XYLT1) is required for TLR3 activation. Moreover, BGN induces the transdifferentiation of valvular interstitial cells into bone-forming osteoblasts through the TLR3-dependent induction of type I IFNs. It is intriguing that Bgn-/-, Tlr3-/-, and Ifnar1-/- mice are protected against CAVD and display impaired bone formation. Meta-analysis of 2 large-scale cohorts with >300 000 individuals reveals that genetic variation at loci relevant to the XYLT1-BGN-TLR3-interferon-α/ß receptor alpha chain (IFNAR) 1 pathway is associated with CAVD in humans. CONCLUSIONS: This study identifies the BGN-TLR3-IFNAR1 axis as an evolutionarily conserved pathway governing calcification of the aortic valve and reveals a potential therapeutic target to prevent CAVD.

Identification of congenital aortic valve malformations in juvenile natriuretic peptide receptor 2-deficient mice using high-frequency ultrasound.

Mouse models of congenital aortic valve malformations are useful for studying disease pathobiology, but most models have incomplete penetrance [e.g., ∼2 to 77% prevalence of bicuspid aortic valves (BAVs) across multiple models]. For longitudinal studies of pathologies associated with BAVs and other congenital valve malformations, which manifest over months in mice, it is operationally inefficient, economically burdensome, and ethically challenging to enroll large numbers of mice in studies without first identifying those with valvular abnormalities. To address this need, we established and validated a novel in vivo high-frequency (30 MHz) ultrasound imaging protocol capable of detecting aortic valvular malformations in juvenile mice. Fifty natriuretic peptide receptor 2 heterozygous mice on a low-density lipoprotein receptor-deficient background (Npr2+/-;Ldlr-/-; 32 males and 18 females) were imaged at 4 and 8 wk of age. Fourteen percent of the Npr2+/-;Ldlr-/- mice exhibited features associated with aortic valve malformations, including 1) abnormal transaortic flow patterns on color Doppler (recirculation and regurgitation), 2) peak systolic flow velocities distal to the aortic valves reaching or surpassing ∼1,250 mm/s by pulsed-wave Doppler, and 3) putative fusion of cusps along commissures and abnormal movement elucidated by two-dimensional (2-D) imaging with ultrahigh temporal resolution. Valves with these features were confirmed by ex vivo gross anatomy and histological visualization to have thickened cusps, partial fusions, or Sievers type-0 bicuspid valves. This ultrasound imaging protocol will enable efficient, cost effective, and humane implementation of studies of congenital aortic valvular abnormalities and associated pathologies in a wide range of mouse models.NEW & NOTEWORTHY We developed a high-frequency ultrasound imaging protocol for diagnosing congenital aortic valve structural abnormalities in 4-wk-old mice. Our protocol defines specific criteria to distinguish mice with abnormal aortic valves from those with normal tricuspid valves using color Doppler, pulsed-wave Doppler, and two-dimensional (2-D) imaging with ultrahigh temporal resolution. This approach enables early identification of valvular abnormalities for efficient and ethical experimental design of longitudinal studies of congenital valve diseases and associated pathologies in mice.

Autotaxin inhibition attenuates the aortic valve calcification by suppressing inflammation-driven fibro-calcific remodeling of valvular interstitial cells.

BACKGROUND: Patients with fibro-calcific aortic valve disease (FCAVD) have lipid depositions in their aortic valve that engender a proinflammatory impetus toward fibrosis and calcification and ultimately valve leaflet stenosis. Although the lipoprotein(a)-autotaxin (ATX)-lysophosphatidic acid axis has been suggested as a potential therapeutic target to prevent the development of FCAVD, supportive evidence using ATX inhibitors is lacking. We here evaluated the therapeutic potency of an ATX inhibitor to attenuate valvular calcification in the FCAVD animal models. METHODS: ATX level and activity in healthy participants and patients with FCAVD were analyzed using a bioinformatics approach using the Gene Expression Omnibus datasets, enzyme-linked immunosorbent assay (ELISA), immunohistochemistry, and western blotting. To evaluate the efficacy of ATX inhibitor, interleukin-1 receptor antagonist-deficient (Il1rn-/-) mice and cholesterol-enriched diet-induced rabbits were used as the FCAVD models, and primary human valvular interstitial cells (VICs) from patients with calcification were employed. RESULTS: The global gene expression profiles of the aortic valve tissue of patients with severe FCAVD demonstrated that ATX gene expression was significantly upregulated and correlated with lipid retention (r = 0.96) or fibro-calcific remodeling-related genes (r = 0.77) in comparison to age-matched non-FCAVD controls. Orally available ATX inhibitor, BBT-877, markedly ameliorated the osteogenic differentiation and further mineralization of primary human VICs in vitro. Additionally, ATX inhibition significantly attenuated fibrosis-related factors' production, with a detectable reduction of osteogenesis-related factors, in human VICs. Mechanistically, ATX inhibitor prohibited fibrotic changes in human VICs via both canonical and non-canonical TGF-ß signaling, and subsequent induction of CTGF, a key factor in tissue fibrosis. In the in vivo FCAVD model system, ATX inhibitor exposure markedly reduced calcific lesion formation in interleukin-1 receptor antagonist-deficient mice (Il1rn-/-, P = 0.0210). This inhibition ameliorated the rate of change in the aortic valve area (P = 0.0287) and mean pressure gradient (P = 0.0249) in the FCAVD rabbit model. Moreover, transaortic maximal velocity (Vmax) was diminished with ATX inhibitor administration (mean Vmax = 1.082) compared to vehicle control (mean Vmax = 1.508, P = 0.0221). Importantly, ATX inhibitor administration suppressed the effects of a high-cholesterol diet and vitamin D2-driven fibrosis, in association with a reduction in macrophage infiltration and calcific deposition, in the aortic valves of this rabbit model. CONCLUSIONS: ATX inhibition attenuates the development of FCAVD while protecting against fibrosis and calcification in VICs, suggesting the potential of using ATX inhibitors to treat FCAVD.

Valvular heart disease in patients with cardiac amyloidosis.

Cardiac amyloidosis (CA) is an underdiagnosed condition caused by the deposition of misfolded proteins, namely immunoglobulin light chains and transthyretin, in the extracellular spaces of the heart. Any cardiovascular structure can be affected by amyloid infiltration, including the valves. Amyloid accumulation within the cardiac valves may lead to their structural and functional impairment, with a profound impact on patients' prognosis and quality of life. The most common forms of valvular disease in CA are aortic stenosis (AS), mitral regurgitation (MR), and tricuspid regurgitation (TR). CA and AS share similar risk factors, disease mechanisms, and remodeling patterns, which make their diagnosis particularly challenging. Patients with both CA and AS experience worse outcomes than CA or AS alone, and transcatheter aortic valve replacement may represent a useful therapeutic strategy in this population. Data on MR and TR are quite limited and mainly coming from case reports or small series. This review paper will summarize our current understanding on the epidemiology, disease mechanisms, echocardiographic features, clinical implications, and therapeutic options of AS, MR, and TR in patients with CA.

Bilateral Harmony™ valve placement in branch pulmonary arteries.

While newer self-expanding pulmonic valves were primarily designed for larger right ventricular outflow tracks, there are instances where even larger anatomies cannot accommodate these devices. In this report, we describe the successful implantation of two Harmony™ valves in bilateral branch pulmonary arteries after exhausting other options.

Management of severe aortic stenosis in the presence of an 8 mm right coronary stent protrusion.

Management of a protruding coronary stent into the aortic root in patients undergoing evaluation for transcatheter aortic valve replacement can be challenging. We describe a patient treated with stent trimming and surgical aortic valve replacement, highlighting the importance of a multidisciplinary evaluation and selection process in this complex scenario.

Simplified balloon-BASILICA: A different perspective.

Nowadays, the long-life management of patients with aortic stenosis has emerged as one of the most debated issues. Transcatheter aortic valve replacement is more frequently performed in younger patients with lower surgical risk, and also the number of valve-in-valve (ViV) procedures has increased in the last few years. However, coronary obstruction is the most dreadful complication related to this procedure. To prevent coronary obstruction in the context of transcatheter aortic ViV implantation, the BASILICA (bioprosthetic or native aortic scallop intentional laceration to prevent iatrogenic coronary artery obstruction) technique was developed. Although effective, BASILICA is complex and time-consuming. Hence, simpler, reproducible, and faster strategies are desirable. Here we present a promising simplified BASILICA technique employing an Armada Balloon to perform the leaflet laceration.

Mitral valve-in-valve with 4D intracardiac echocardiography: Procedural and imaging technique.

Transcatheter mitral valve-in-valve (ViV) has emerged as a safe and effective therapeutic option for patients with a degenerated mitral bioprosthesis. As procedural techniques mature and operator experience improve, there is a push to adopt a "minimalist" approach of using conscious sedation instead of general anesthesia for faster recovery. The heavy reliance on fluoroscopy for ViV deployment makes feasible the use of intracardiac echocardiography (ICE) instead of transesophageal echocardiography for other procedural imaging requirements. We hereby use a case example to illustrate a step-by-step approach of using four-dimensional ICE to guide transcatheter mitral ViV under conscious sedation.

The PIGTAIL paradigm for a fast and safe transfemoral transcatheter aortic valve replacement.

Transfemoral transcatheter aortic valve replacement is the preferred primary access route whenever possible. Despite advancements in expertise and delivery system profiles, complications associated with the primary femoral access still significantly affect procedural morbidity and outcomes. The current standard for accurate main access planning involves proper preprocedural evaluation guided by computed tomography. Several baseline clinical and anatomical features serve as predictors for the risk of vascular injury occurring during or after transcatheter aortic valve replacement. In this paper, we aimed at reviewing the most up-to-date knowledge of the topic for a safe transfemoral access approach according to a paradigm we have called "PIGTAIL."

Ventriculo-arterial uncoupling with an impella assisted HVAD: The p-D LVAD.

This paper presents the novel use of a temporary percutaneous ventricular assist device (pVAD) in a 51-year-old man with an implanted durable left ventricular assist device (d-LVAD). The pre-existing left ventricular assist device was unable to successfully unload the left ventricle, and the addition of the temporary pVAD achieved successful unloading as well as a decrease in pulmonary artery pressures without compromising the function of the right ventricle allowing safe UNOS listing for orthotopic heart transplantation.

Computed tomography derived anatomical predictors of vascular access complications following transfemoral transcatheter aortic valve implantation: A systematic review.

BACKGROUND: Vascular complications after percutaneous transfemoral transcatheter aortic valve implantation (TAVI) are associated with adverse clinical outcomes and remain a significant challenge. AIMS: The purpose of this review is to synthesize the existing evidence regarding the iliofemoral artery features predictive of vascular complications after TAVI on pre-procedural contrast-enhanced multidetector computed tomography (MDCT). METHODS: A systematic search was performed in Embase and Medline (Pubmed) databases. Studies of patients undergoing transfemoral TAVI with MDCT were included. Studies with only valve-in-valve TAVI, planned surgical intervention and those using fluoroscopic assessment were excluded. Data on study cohort, procedural characteristics and significant predictors of vascular complications were extracted. RESULTS: We identified 23 original studies involving 8697 patients who underwent TAVI between 2006 and 2020. Of all patients, 8514 (97.9%) underwent percutaneous transfemoral-TAVI, of which 8068 (94.8%) had contrast-enhanced MDCT. The incidence of major vascular complications was 6.7 ± 4.1% and minor vascular complications 26.1 ± 7.8%. Significant independent predictors of major and minor complications related to vessel dimensions were common femoral artery depth (>54 mm), sheath-to-iliofemoral artery diameter ratio (>0.91-1.19), sheath-to-femoral artery diameter ratio (>1.03-1.45) and sheath-to-femoral artery area ratio (>1.35). Substantial iliofemoral vessel tortuosity predicted 2-5-fold higher vascular risk. Significant iliofemoral calcification predicted 2-5-fold higher risk. The iliac morphology score was the only hybrid scoring system with predictive value. CONCLUSIONS: Independent iliofemoral predictors of access-site complications in TAVI were related to vessel size, depth, calcification and tortuosity. These should be considered when planning transfemoral TAVI and in the design of future risk prediction models.

Transcatheter pulmonary valve replacement in surgically-created double-barrel right ventricular outflow tracts: A single center case-series.

This manuscript describes the feasibility and approach to the assessment and performance of transcatheter pulmonary valve replacement (tPVR) in patients with surgically-created "double-barrel" right ventricular outflow tracts (RVOT). Patients with tetralogy of Fallot may have coronary anomalies which prohibit the performance of traditional tetralogy of Fallot repair. In certain cases, this may necessitate the placement of a right ventricle to pulmonary artery conduit in addition to the native RVOT, which is left in situ, creating so-called "double-barrel" RVOTs. When these patients develop RVOT dysfunction later in life, they would typically be referred for reoperation due to concerns for risk of coronary compression associated with a transcatheter approach. However, whether a transcatheter approach with valve replacement in the native RVOT is feasible or safe is unknown. This was a retrospective review of patients with a surgically created "double-barrel" RVOTs who underwent cardiac catheterization for assessment of tPVR at Boston Children's Hospital. From July 2012 to July 2022, there were four patients with "double-barrel" RVOTs who underwent assessment for tPVR. The age at catheterization ranged between 22 and 39 years. In three out of four patients, coronary compression testing was negative. These three patients had successful tPVR in the native RVOT. At follow up, all three patients were free of greater than mild regurgitation by echocardiogram and had a maximum instantaneous gradient across the RVOT ranging between 20 and 33 mmHg. Performance of tPVR in patients with surgically created "double-barrel" RVOTs is feasible. The safety of this procedure depends crucially on coronary artery assessment at all stages.

Long-term function of a novel autologous transcatheter pulmonary heart valve implant in an adult animal model.

BACKGROUND: Current heart valve implants entail major disadvantages in the treatment for younger patients or those with congenital heart defects. AIM: Evaluation of novel transcatheter pulmonary valve implant made from autologous pericardium with natural crosslinking agent in an in vitro setup and in vivo animal model METHODS: Valves were tested in a pulse duplicator according to ISO-standard 5840. For in vivo studies computer tomography was performed to measure sheep's native pulmonary valve dimensions. Pericardium was harvested by thoracotomy, personalized implants were manufactured and deployed in pulmonary valve position of the same sheep. Every 3 months implant functionality was evaluated by intracardiac echocardiography, intracardiac pressure measurements and cardiac magnetic resonance imaging (cMRI). Implants were explanted for macroscopic and histological examination. RESULTS: In vitro experiments showed compliance with regulatory requirements in terms of valve opening and insufficiency. Five sheep successfully received an autologous valve implant. Two animals had to be euthanized due to trauma sustained in the stable. Long-term valve function was excellent in three out of four animals with median implant cMRI regurgitation fraction of 9% (n = 4) at 3 months, 8% (n = 3) at 6, 8% (n = 3) at 9, 12% (n = 3) at 13, 8% (n = 2) at 17% and 8% (n = 2) at 20.5 months after implantation. Despite good adherence to neighboring tissue and endothelization, histological assessment revealed some signs of degeneration. CONCLUSION: Transcatheter pulmonary valve implants showed promising function for up to 20.5 months encouraging research to further improve this approach.

Recurrent hypo-attenuated leaflet thickening after TAVR: Clinical implications.

Subclinical bioprosthetic valve thrombosis (BPVT) is a relatively common finding in asymptomatic patients during follow-up imaging. However, its clinical significance is unclear. Data from registries associate BPVT with elevated valve gradients, thromboembolic complications, recurrence, and valve degeneration. Given the dynamic nature of the disease process, management is challenging. The duration of anticoagulation is unpredictable, and the need for frequent monitoring of BPVT, even in subclinical scenarios, is unclear. Our report is shedding the light on the clinical implications BPVT.

Clinical correlates of circulating small dense low-density lipoproteins in acute infective endocarditis.

BACKGROUND AND AIM: Infective endocarditis (IE) is a complex thrombo-inflammatory disorder, the pathogenesis of which involves a multifaceted interplay between vascular damage and bacterial virulence factors. This study aimed to assess the prognostic role of small dense low-density lipoprotein (sdLDL) cholesterol in patients with IE and its correlation with various disease-related features. METHODS: A cohort of 198 patients with definite IE was included in this study. Clinical, laboratory, and echocardiographic parameters were meticulously analyzed, with a specific focus on comorbidities. sdLDL levels were measured using stored plasma samples obtained upon admission during the acute phase of the disease. RESULTS: The median level of sdLDL was 24 mg/dL [with an interquartile range of 17.9-35.2 mg/dL], and this value showed a statistically significant positive correlation with LDL/HDL cholesterol and triglycerides (p < 0.01 for all). Furthermore, a remarkable inverse correlation between C-reactive protein and D-dimer levels was observed (p < 0.0001). Univariate analysis revealed that patients with sdLDL levels ≤ 24 mg/dL had 2.75 times higher odds of in-hospital mortality (95% Confidence Interval:1.08-6.98, p = 0.031). In addition, nonsurvivors had significantly lower median sdLDL levels (19.7 vs. 26.0 mg/dL, p = 0.041). Lower sdLDL levels were also associated with embolic complications, larger vegetation size, and positive blood cultures for Staphylococci (p = 0.019, p = 0.022, and p < 0.001, respectively). CONCLUSIONS: Low circulating sdLDL levels in the acute phase of IE were significantly correlated with unfavorable clinical outcomes. These results suggest that the sdLDL level may serve as an important marker of disease severity in IE and may represent a link between vascular damage, embolic complications, and disease progression.