Quantitative Computed Tomography Angiography for the Evaluation of Valvular Fibrocalcific Volume in Aortic Stenosis.

BACKGROUND: Aortic stenosis (AS) is characterized by calcification and fibrosis. The ability to quantify these processes simultaneously has been limited with previous imaging methods. OBJECTIVES: The purpose of this study was to evaluate the aortic valve fibrocalcific volume by computed tomography (CT) angiography in patients with AS, in particular, to assess its reproducibility, association with histology and disease severity, and ability to predict/track progression. METHODS: In 136 patients with AS, fibrocalcific volume was calculated on CT angiograms at baseline and after 1 year. CT attenuation distributions were analyzed using Gaussian-mixture-modeling to derive thresholds for tissue types enabling the quantification of calcific, noncalcific, and fibrocalcific volumes. Scan-rescan reproducibility was assessed and validation provided against histology and in an external cohort. RESULTS: Fibrocalcific volume measurements took 5.8 ± 1.0 min/scan, demonstrating good correlation with ex vivo valve weight (r = 0.51; P < 0.001) and excellent scan-rescan reproducibility (mean difference -1%, limits of agreement -4.5% to 2.8%). Baseline fibrocalcific volumes correlated with mean gradient on echocardiography in both male and female participants (rho = 0.64 and 0.69, respectively; both P < 0.001) and in the external validation cohort (n = 66, rho = 0.58; P < 0.001). The relationship was driven principally by calcific volume in men and fibrotic volume in women. After 1 year, fibrocalcific volume increased by 17% and correlated with progression in mean gradient (rho = 0.32; P = 0.003). Baseline fibrocalcific volume was the strongest predictor of subsequent mean gradient progression, with a particularly strong association in female patients (rho = 0.75; P < 0.001). CONCLUSIONS: The aortic valve fibrocalcific volume provides an anatomic assessment of AS severity that can track disease progression precisely. It correlates with disease severity and hemodynamic progression in both male and female patients.

TAVR for Severe Aortic Valve Stenosis with LVOT Stenosis: A Case Report.

Transcatheter aortic valve replacement (TAVR) has been recently indicated for the treatment of patients with severe aortic stenosis in all risk profiles. At present, TAVR has become mature at home and abroad, but the relevant experience is deficient in the treatment of aortic valve stenosis with outflow tract stenosis. One case of a high-risk surgical patient was included in this paper who suffered from severe aortic valve stenosis with left ventricular outflow tract (LVOT) stenosis. In this case, TAVR was performed with deep implantation of a new valve and both aortic valve stenosis and LVOT stenosis were treated through a single TAVR procedure. This case highlights the vital role of such treatment in dealing with both aortic valve stenosis and LVOT stenosis through a single TAVR procedure, thus providing valuable information for similar cases.

Brachiocephalic Artery Access Without Sternotomy in Older Asian Patients Undergoing Transcatheter Aortic Valve Replacement.

There are numerous approaches for transcatheter aortic valve replacement (TAVR); however, access-related complications remain a point of concern. We analyzed consecutive patients who underwent TAVR for severe aortic stenosis via the brachiocephalic artery (BCA) without sternotomy (TBc group, n = 10) and via the trans-ascending aortic (TAo group, n = 8). The median BCA diameter and distance between the access point and suprasternal notch or superior margin of the clavicle were 11.3 mm and 8.3 mm, respectively. No patients in the TBc group underwent a partial sternotomy. Compared with the TAo group, the TBc group exhibited a shorter mean procedure time and lower blood loss volume as well as shorter duration of hospitalization. TAVR through the BCA may be a safe and feasible alternative for ascending aorta access. Studies with longer follow-up analysis and more patients are warranted to confirm our findings.

Management of bicuspid aortic valve disease in the transcatheter aortic valve implantation era.

In an era of rapidly expanding use of transcatheter aortic valve implantation (TAVI), the management of patients with bicuspid aortic valve (BAV) disease is far less well established than in those with trileaflet anatomy. Results of isolated surgical aortic valve replacement are excellent in suitable patients, and surgery also allows treatment of concomitant pathology of the aortic root and ascending aorta that is frequently encountered in this cohort. Conversely, TAVI provides an excellent alternative in older patients who may be unsuitable for surgery, although outcomes in BAV disease have only been reported in relatively small non-randomised series. Here, we discuss the pertinent literature on this topic and outline contemporary interventional treatment options in this challenging setting.

Physical Frailty and the Risk of Degenerative Valvular Heart Disease.

Background and Objectives: The relationship between physical frailty, age-related conditions, and the incidence of degenerative valvular heart disease (VHD) remains unclear. This study aimed to investigate the potential association between physical frailty and the development of degenerative VHD. Research Design and Methods: Participants from the UK Biobank who were initially free of VHD and heart failure were categorized into 3 groups based on the frailty phenotype: non-frailty, pre-frailty, and frailty. The frailty phenotype was determined by evaluating the following 5 components: weight loss, exhaustion, reduced physical activity, slow gait speed, and low grip strength. The incidence of degenerative VHD, including mitral valve regurgitation (MR), aortic valve regurgitation (AR), and aortic valve stenosis (AS), was assessed using hospital admission or death registries. Results: Among the 331 642 participants, 11 885 (3.6%) exhibited frailty and 143 379 (43.2%) were categorized as pre-frailty. During a median follow-up of 13.8 years, there were 3 684 MR, 1 205 AR, and 3 166 AS events. Compared to non-frailty participants, those with pre-frailty and frailty showed significantly increased risks for MR (hazard ratio [HR], HRpre-frailty:1.19, 95% confidence interval [CI]: 1.11-1.28; HRfrailty: 1.50, 95% CI: 1.30-1.74), AR (HRpre-frailty:1.19, 95% CI: 1.05-1.34; HRfrailty: 1.58, 95% CI: 1.22-2.04), and AS (HRpre-frailty:1.19, 95% CI: 1.11-1.29; HRfrailty: 1.74, 95% CI: 1.51-2.00). Among the 5 components, slow gait speed showed the strongest association with the risk of various types of VHD (HRMR: 1.50, 95% CI: 1.34-1.65; HRAR: 1.50, 95% CI: 1.24-1.80; HRAS: 1.46, 95% CI: 1.32-1.62), followed by exhaustion, low grip strength, and weight loss. Discussion and Implications: Pre-frailty and frailty were associated with a higher risk of all 3 types of degenerative VHD. Early detection and intervention for pre-frailty and frailty in middle-aged and older individuals may assist in preventing or delaying the onset of degenerative VHD.

Insulin-like Growth Factor-Binding Protein 2 in Severe Aortic Valve Stenosis and Pulmonary Hypertension: A Gender-Based Perspective.

Severe aortic valve stenosis (AS) and pulmonary hypertension (PH) are life-threatening cardiovascular conditions, necessitating early detection and intervention. Recent studies have explored the role of Insulin-like Growth Factor-Binding Protein 2 (IGF-BP2) in cardiovascular pathophysiology. Understanding its involvement may offer novel insights into disease mechanisms and therapeutic targets for these conditions. A total of 102 patients (46 female, 56 male) with severe AS undergoing a transcatheter aortic valve replacement (TAVR) in a single-center study were classified using echocardiography tests to determine systolic pulmonary artery pressure (sPAP) and the presence (sPAP ≥ 40 mmHg) or absence (sPAP < 40 mmHg) of PH. Additionally, serial laboratory determinations of IGF-BP2 before, and at 24 h, 96 h, and 3 months after intervention were conducted in all study participants. Considering the entire cohort, patients with PH had significant and continuously higher serum IGF-BP2 concentrations over time than patients without PH. After subdivision by sex, it could be demonstrated that the above-mentioned results were only verifiable in males, but not in females. In the male patients, baseline IGF-BP2 levels before the TAVR was an isolated risk factor for premature death after intervention and at 1, 3, and 5 years post-intervention. The same was valid for the combination of male and echocardiographically established PH patients. The predictive role of IGF-BP2 in severe AS and concurrent PH remains unknown. A more profound comprehension of IGF-BP2 mechanisms, particularly in males, could facilitate the earlier consideration of the TAVR as a more effective and successful treatment strategy.

Unusual Presentation of De Winter's Sign Due to Bezold-Jarisch Reflex in a Patient With Severe Aortic Valve Stenosis.

The de Winter electrocardiogram (ECG) pattern, marked by upsloping ST depression in leads V2-V6, ST elevation in lead aVR, and tall symmetric T waves, typically indicates left anterior descending artery (LAD) occlusion. Traditionally linked to LAD occlusion, it is rare in severe aortic stenosis and the Bezold-Jarisch reflex (BJR). We report an 83-year-old man with severe aortic stenosis who developed hypotension due to bleeding and exhibited the de Winter ECG pattern. This case highlights how severe aortic stenosis and BJR can lead to significant hemodynamic instability and ischemic ECG changes, resolving after hemodynamic stabilization.

Investigation of von Willebrand factor multimer abnormalities before and after aortic valve replacement using the Hydragel-5 assay.

BACKGROUND: Severe aortic stenosis (sAS) is associated with acquired von Willebrand syndrome (AVWS) by loss of high-molecular-weight multimers (HMWM) of von Willebrand factor (VWF), potentially resulting in perioperative bleeding. Analysis of VWF multimers remains challenging. Recently, the new, rapid Hydragel 5 assay has been developed, using electrophoretic protein separation for dividing VWF-multimers into low (LMWM), intermediate (IMWM), and HMWM, the hemostatically active part of VWF. Here, we evaluated its impact on predicting blood loss in presence of AVWS after surgical aortic valve replacement (SAVR). METHODS: We prospectively examined 52 patients (age: 68 ± 7 years; 54 % male) admitted to SAVR. They were divided in two groups (A: normal VWF, n = 28; B: abnormal VWF, n = 24, defined as VWF-activity/antigen (VWF:Ac/Ag)-ratio < 0.7 and/or HMWM loss). Blood samples and echocardiographic data were collected before, seven days and three months after SAVR. Blood loss and transfusions were recorded. RESULTS: Baseline characteristics and clinical data were similar in both groups. HMWM loss was present in 38.5 % of all patients. HMWM, the VWF:Ac/Ag- and HMWM/(IMWM+LMWM)-ratios were significantly decreased preoperatively in group B but normalized after SAVR. Bleeding, re-thoracotomy and transfusion rates were comparable. HMWM loss was inversely correlated with the peak aortic gradient (Pmax) and positively with the aortic valve area (AVA), while HMWM/(IMWM+LMWM)-ratio negatively correlated with the mean aortic gradient (Pmean). CONCLUSION: HMWM and HMWM/(IMWM+LMWM)-ratio inversely correlate with severity of AS and normalize after SAVR. The Hydragel-5 assay's might be valuable for routine diagnostics to assess bleeding risk and postoperative normalization of AS and VWF abnormalities in SAVR patients.

Bicuspid Aortic Valve Function and Aortopathy on Presentation and Progression in Children: Does Sex Difference Have Any Implications?

Bicuspid aortic valve (BAV) is the most common congenital heart defect. It can be accompanied by aortic regurgitation or stenosis with aortopathies. Studies in adults showed a sex difference, but there are limited number of reports in the pediatric population. To evaluate the difference in bicuspid aortic valve morphology and functionality between sexes, and the presence and progression of aortopathies, a retrospective chart review study was performed at a tertiary referral care center in the Midwest. In our study, we analyzed a cohort of 476 pediatric patients diagnosed with BAV who presented between January 2007 and February 2018. During the follow-up period spanning 2 to 10 years, male patients (n = 314, 66%) had larger aortic valve annulus (AVA) and sinus of Valsalva (SOV) at the time of initial presentation with more likelihood for progression. In the subgroup analysis, the larger SOV in males was observed in isolated BAV patients without genetic syndromes or cardiac malformations, and there were no significant differences between both sexes in the ascending aorta dimension, valve functionality, valve morphology, and the need for intervention in any of the studied groups. As such, these findings may alter the follow-up focus and frequency for patients with BAV, particularly before adulthood, and warrant further studies.

Macrophage Migration Inhibitory Factor Promotes Thromboinflammation and Predicts Fast Progression of Aortic Stenosis.

BACKGROUND: Aortic stenosis (AS) is driven by progressive inflammatory and fibrocalcific processes regulated by circulating inflammatory and valve resident endothelial and interstitial cells. The impact of platelets, platelet-derived mediators, and platelet-monocyte interactions on the acceleration of local valvular inflammation and mineralization is presently unknown. METHODS: We prospectively enrolled 475 consecutive patients with severe symptomatic AS undergoing aortic valve replacement. Clinical workup included repetitive echocardiography, analysis of platelets, monocytes, chemokine profiling, aortic valve tissue samples for immunohistochemistry, and gene expression analysis. RESULTS: The patients were classified as fast-progressive AS by the median ∆Vmax of 0.45 m/s per year determined by echocardiography. Immunohistological aortic valve analysis revealed enhanced cellularity in fast-progressive AS (slow- versus fast-progressive AS; median [interquartile range], 247 [142.3-504] versus 717.5 [360.5-1234]; P<0.001) with less calcification (calcification area, mm2: 33.74 [27.82-41.86] versus 20.54 [13.52-33.41]; P<0.001). MIF (macrophage migration inhibitory factor)-associated gene expression was significantly enhanced in fast-progressive AS accompanied by significantly elevated MIF plasma levels (mean±SEM; 6877±379.1 versus 9959±749.1; P<0.001), increased platelet activation, and decreased intracellular MIF expression indicating enhanced MIF release upon platelet activation (CD62P, %: median [interquartile range], 16.8 [11.58-23.8] versus 20.55 [12.48-32.28], P=0.005; MIF, %: 4.85 [1.48-9.75] versus 2.3 [0.78-5.9], P<0.001). Regression analysis confirmed that MIF-associated biomarkers are strongly associated with an accelerated course of AS. CONCLUSIONS: Our findings suggest a key role for platelet-derived MIF and its interplay with circulating and valve resident monocytes/macrophages in local and systemic thromboinflammation during accelerated AS. MIF-based biomarkers predict an accelerated course of AS and represent a novel pharmacological target to attenuate progression of AS.

Aortic Valve Calcium Score: Applications in Clinical Practice and Scientific Research-A Narrative Review.

In this narrative review, we investigate the essential role played by the computed tomography Aortic Valve Calcium Score (AVCS) in the cardiovascular diagnostic landscape, with a special focus on its implications for clinical practice and scientific research. Calcific aortic valve stenosis is the most prevalent type of aortic stenosis (AS) in industrialized countries, and due to the aging population, its prevalence is increasing. While transthoracic echocardiography (TTE) remains the gold standard, AVCS stands out as an essential complementary tool in evaluating patients with AS. The advantage of AVCS is its independence from flow; this allows for a more precise evaluation of patients with discordant findings in TTE. Further clinical applications of AVCS include in the assessment of patients before transcatheter aortic valve replacement (TAVR), as it helps in predicting outcomes and provides prognostic information post-TAVR. Additionally, we describe different AVCS thresholds regarding gender and the anatomical variations of the aortic valve. Finally, we discuss various scientific studies where AVCS was applied. As AVCS has some limitations, due to the pathophysiologies of AS extending beyond calcification and gender differences, scientists strive to validate contrast-enhanced AVCS. Furthermore, research on developing radiation-free methods of measuring calcium content is ongoing.

Genetic proxy of lipid-lowering drugs and calcific aortic valve stenosis: A Mendelian randomization study.

Background: Lipid metabolism plays an important role in the pathogenesis and development of calcific aortic valve stenosis. Our aim was to evaluate the causal effect of lipid-lowering drugs, such as low-density lipoprotein cholesterol (LDL-C) lowering and triglyceride lowering drugs, on the outcome of aortic valve stenosis using a two-sample Mendelian randomization (MR) study. Methods: We used two genetic tools to represent the exposure of lipid-lowering drugs, including expression quantitative trait loci for the expression of drug target genes, and genetic variants within or near drug target genes that are associated with LDL-C and triglyceride concentrations from Genome-Wide Association Studies (GWAS). Effect estimates were calculated using summary-data-based MR (SMR) and inverse-variance-weighted MR (IVW-MR) analysis. Results: Based on the results of SMR and IVW-MR analysis, LDL-C-lowering PCSK9 inhibitors have potential in reducing the risk of aortic valve stenosis (for SMR, OR: 1.044; 95%CI: 1.002-1.404; P = 0.047; for IVW-MR, OR: 1.647, 95%CI: 1.316-2.062, P < 0.001). However, no significant association was observed between triglyceride target gene expression, as well as triglyceride-lowering drugs, and aortic valve stenosis. Conclusion: This two-sample drug-targeted MR study suggests a potential causal relationship between PCSK9 inhibitors and the reduction of calcific aortic valve stenosis risk.

Type 2 Diabetes, Circulating Metabolites, and Calcific Aortic Valve Stenosis: A Mendelian Randomization Study.

Epidemiological studies have shown an association between type 2 diabetes (T2D) and calcific aortic valve stenosis (CAVS), but the potential causal relationship and underlying mechanisms remain unclear. Therefore, we conducted a two-sample and two-step Mendelian randomization (MR) analysis to evaluate the association of T2D with CAVS and the mediating effects of circulating metabolites and blood pressure using genome-wide association study (GWAS) summary statistics. The inverse variance weighted (IVW) method was used for the primary MR analysis, and comprehensive sensitivity analyses were performed to validate the robustness of the results. Our results showed that genetically predicted T2D was associated with increased CAVS risk (OR 1.153, 95% CI 1.096-1.214, p < 0.001), and this association persisted even after adjusting for adiposity traits in multivariable MR analysis. Furthermore, the two-step MR analysis identified 69 of 251 candidate mediators that partially mediated the effect of T2D on CAVS, including total branched-chain amino acids (proportion mediated: 23.29%), valine (17.78%), tyrosine (9.68%), systolic blood pressure (8.72%), the triglyceride group (6.07-11.99%), the fatty acid group (4.78-12.82%), and the cholesterol group (3.64-11.56%). This MR study elucidated the causal impact of T2D on CAVS risk independently of adiposity and identified potential mediators in this association pathways. Our findings shed light on the pathogenesis of CAVS and suggest additional targets for the prevention and intervention of CAVS attributed to T2D.

Mitral complex geometric changes aggravate mitral stenosis after transcatheter aortic valve replacement.

Severe aortic valve stenosis (AS) often coexists with mitral valve stenosis (MS). MS aggravation after transcatheter aortic valve replacement (TAVR) is common, and its etiology is multifactorial. We hypothesized that geometric changes in the mitral complex (mitral valvular and annular deformities) are adjunctive factors aggravating MS after TAVR, particularly in older adults with a smaller left ventricle (LV). This study aimed to evaluate the mitral complex geometric changes before and after TAVR and to assess the important predictors of MS aggravation after TAVR. This retrospective study enrolled consecutive adult patients who underwent TAVR and surgical AVR (SAVR) for severe AS. The mitral valve area (MVA), the angle between the anterior mitral valve leaflet (AMVL) and left ventricular outflow tract (LVOT), AMVL length, mitral annular diameter, presence of mitral annular calcification, and LV size were evaluated using transthoracic echocardiography. This study included 258 patients who underwent TAVR and SAVR. MVA index decreased from 2.3 ± 0.6 cm² to 1.9 ± 0.5 cm² in the TAVR group. The angle between the AMVL and LVOT was 56.3 ± 9.7° preoperatively and increased to 67.3 ± 11.5° after TAVR. In multivariate analysis, the most important predictive factors of MS aggravation after TAVR were a smaller mitral annular diameter, restricted AMVL mobility, and implantation depth (odds ratio: 4.5, 5.3,3.0; 95% confidence interval: 1.6-14, 1.9-17, 1.0-8.9; and p = 0.005, p = 0.001, p = 0.042, respectively). The reduction in MVA after TAVR was related to the restriction of AMVL opening, depth of implantation and narrowing of the mitral annulus.

Antithrombotic Therapy in Patients Undergoing Transcatheter Aortic Valve Implantation.

Transcatheter aortic valve implantation (TAVI) now represents the mainstay of treatment for severe aortic stenosis. Owing to its exceptional procedural efficacy and safety, TAVI has been extended to include patients at lower surgical risk, thus now encompassing a diverse patient population receiving this treatment. Yet, long-term outcomes also depend on optimal medical therapy for secondary vascular prevention, with antithrombotic therapy serving as the cornerstone. Leveraging data from multiple randomized controlled trials, the current guidelines generally recommend single antithrombotic therapy, with either single antiplatelet therapy (SAPT) or oral anticoagulation (OAC) alone in those patients without or with atrial fibrillation, respectively. Yet, individualization of this pattern, as well as specific case uses, may be needed based on individual patient characteristics and concurrent procedures. This review aims to discuss the evidence supporting antithrombotic treatments in patients treated with TAVI, indications for a standardized treatment, as well as specific considerations for an individualized approach to treatment.

Association between Systolic Blood Pressure Variability and Incident Aortic Stenosis.

Background: This study investigated the potential link between blood pressure variability (BPV) and the incidence of aortic stenosis (AS) using Korean National Health Insurance Service data from 2002 to 2019. Methods: We collected annual systolic blood pressure variability (SBPV) measurements consisting of three consecutive blood pressure readings each year over three years. The obtained SBPV data was divided into five quantiles, with the highest quintile representing a high fluctuation of blood pressure. Results: Analyzing 9,341,629 individuals with a mean age of 40.7 years, the study found 3981 new AS diagnoses during an average 8.66-year follow-up. Independent predictors for AS included higher blood pressure levels and elevated systolic blood pressure variability (SBPV). The hazard ratios (HR) for different SBPV quintiles compared to the reference (1st quintile) were as follows: 2nd quintile HR 1.09 (p = 0.18), 3rd quintile HR 1.13 (p = 0.04), 4th quintile HR 1.13 (p = 0.04), and 5th quintile HR 1.39 (p < 0.001). Conclusion: Our findings suggest that both hypertension and high fluctuations in SBP during consecutive visits are associated with an increased risk of incident AS. These results emphasize the importance of blood pressure management and stability in the prevention of AS.