Valve Calcification Research Articles

Prevalence of heart valve disease and left ventricular systolic dysfunction in a multi-ethnic, migrant community

Abstract Introduction Clinically significant valvular heart disease (VHD) affects 13.3% of individuals aged 75 and older, while left ventricular systolic dysfunction (LVSD) is seen in 2% of those aged 85 and older, and 3.5% of those aged 65 and older but most data comes from rural/suburban areas with predominantly Caucasian populations. Data on these diseases in urban, ethnically diverse areas with high migrant populations is lacking. Purpose This quality improvement project aimed to establish the prevalence of left-sided valve disease and LVSD by conducting community-based handheld echocardiography detection in an urban, multi-ethnic community. Methods Patients over 65 without known left-sided heart valve disease or heart failure, across four GP practices and one vaccination centre using handheld ultrasound device (Vscan Extend). The protocol included an abbreviated dataset with colour flow and three standard echocardiography views. All studies were reviewed and adjudicated by an independent expert. Those patients adjudicated to have important disease on handheld detection underwent subsequent comprehensive echocardiography. Results 518 patients were evaluated. Ethnic distribution: 14.4% Caucasian, 51.6% Indian, 0.2% Chinese, 14% Pakistani, 9.7% African, 9.1% other. New diagnoses of left-sided HVD or LVSD were identified in (n=166 ) 32% and (n=10) 2% respectively. Mitral Regurgitation (MR) was most common (n =100, 19.3%), followed by aortic regurgitation (AR) (n =30, 5.8%), aortic stenosis (AS) (n =13, 2.5%), and mitral stenosis (MS) (n =2, 0.4%). LVSD was found in (n=10, 2%). Comprehensive confirmatory echocardiograms were done in 73 patients. Of these mild VHD was observed in n =57 (78%), (mild AR n =27, 37%, mild MR n =31, 45%, and mild AS/aortic sclerosis n =12, 16%). Calcified mitral valve was found in n =3, (4%). Mild LVSD was in n =6, 8%. Moderate to severe HVD was found in n= 12 (16.4%), (MR in 8%, AR in 5% and AS in 2.7%) and moderate to severe LVSD in n =3, 4%. Age predicted HVD (OR 1.09, 95% CI 1.06-1.13, p <0.001) and LVSD (OR 1.07, 95% CI 1.01-1.13, p <0.05) while Type 2 diabetes (OR 3.47, 95% CI 0.13-0.83, p <0.05) and ischemic heart disease (IHD) (OR 5.41, 95% CI 2.26-13.11, p <0.001) were predictors for LVSD. There was no relationship between ethnic group and the presence of HVD or LVSD (p values >0.05). Conclusion(s) HVD and LVSD is common in this urban, multi-ethnic community. A Vscan based detection program found a prevalence of any VHD of 32% and LVSD of 2% . Of these 2.3% and 0.6% were moderate to severe (HVD and LVSD). Age was associated with both HVD and LVSD, while T2DM and IHD are associated with LVSD. There was no relationship between ethnicity and either HVD or LVSD. Severity of HVD Ethnicity Distribution

The influence of left-heart myopathy on the diagnosis and treatment of mitral valve stenosis: an in silico trial

Abstract Background The shift in mitral stenosis (MS) aetiology from rheumatic to calcific valve disease, commonly seen in elderly patients with cardiomyopathy, challenges the differentiation between valve- or tissue-related causes of haemodynamic abnormalities. Purpose This study examines the impact of left-heart myopathy on the echocardiographic assessment of MS severity and acute haemodynamic effects following mitral valve (MV) intervention. Methods The CircAdapt model of the human cardiovascular system was used to evaluate the effect of MS on cardiac haemodynamics in a virtual patient cohort with broad ranges of impaired left atrial (LA) function and reduced left ventricular (LV) compliance. Mean gradient (MG) and pressure half-time (PHT) were derived for MS severity assessment, alongside LV and LA pressure traces to quantify the haemodynamic consequence of MV intervention. Results Depending on myocardial abnormalities, the MG varied by only 10%, 5% and 5% for mild, moderate and severe MS, respectively. Reduced LV compliance resulted in disproportionately lower PHT causing overestimation of the PHT-derived MV area up to 1.43 cm2. Following virtual MV intervention for moderate to severe MS, mean left atrial pressure (mLAP) decreased by 50% in presence of healthy myocardium but only 4% for combined LV and LA dysfunction. In patients with reduced LV compliance, LV end-diastolic pressure remained elevated despite MV intervention. Conclusions The virtual patient cohorts indicate that the MG is a robust metric for MS severity regardless of left-heart myopathy, whereas PHT may reveal underlying impaired LV compliance. However, neither MG nor PHT predict changes in mLAP following intervention. Recognizing the significance of distinguishing between increased left-heart pressures driven by valvular or tissue factors is therefore crucial for clinical decision-making. graphical abstract methods

Multimodality imaging analysis of the spectrum of endomyocardial fibrosis involvement in a clinical case series

Abstract Background Endomyocardial fibrosis (EMF) is a rare restrictive heart disease of the tropics. Its etiology is cryptogenic; however, some hypotheses have been described. The clinical course is characterized by the presence of 3 phases (acute, subacute and chronic). Most of the typical features of the disease are identified in the chronic phase. Multimodality imaging allows a presumptive diagnosis and cardiac magnetic resonance imaging (CMR), through its tissue characterization, allows confirmation of the diagnosis. Case summary We present three clinical cases of patients with endomyocardial fibrosis, at different stages of the disease, which constituted a diagnostic challenge. However, it is due to multimodality imaging that a timely and accurate diagnosis is achieved. Conclusion Endomyocardial fibrosis is a rare heart disease with a restrictive phenotype and a poor prognosis. EMF is characterized by apical obliteration with fibrous tissue, of one or both ventricles, and is usually associated with thrombosis, calcification and AV valve insufficiency. TTE is the first-line imaging modality to assess for EMF. CMR, through late gadolinium enhancement, allows tissue characterization and identifies the “Double V sign”, which is pathognomonic of the disease, allowing confirmation of the diagnosis. Therefore, multimodality imaging is essential for the initial and definitive diagnosis of this disease.

Kissing balloon technique as rescue strategy to treat left ventricular outflow tract obstruction after transcatheter mitral valve replacement: a case report

Abstract Background Transcatheter mitral valve replacement (TMVR) has become a viable, minimally invasive treatment for inoperable patients with severe mitral valve disease, particularly among elderly individuals with significant comorbidities. A key complication of TMVR is left ventricular outflow tract (LVOT) obstruction, necessitating various preventive and therapeutic strategies. This report presents a case of severe LVOT obstruction following TMVR and highlights the effective application of the kissing balloon technique as a therapeutic intervention. Case Presentation A 79-year-old female with New York Heart Association class IV dyspnea due to severe mitral stenosis and a high operative risk (STS-PROM score 6.2%) underwent TMVR. Pre-procedural evaluations indicated significant mitral valve calcification and a mitral valve area of 0.9 cm². After successful TMVR deployment, post-implantation echocardiography revealed an LVOT pressure gradient of 53/85 mmHg, prompting the use of the kissing balloon technique, which reduced the gradient to 28 mmHg. Follow-up assessments showed normal mitral valve function and stable LVOT gradients during short-term follow-up throughout the patient’s hospital stay. Discussion LVOT obstruction is a potentially life-threatening complication of TMVR, often associated with high mortality rates due to hemodynamic impairment. This complication can arise from various anatomical factors and valve positioning issues. Several strategies have been developed to address LVOT obstruction, including the laceration of the anterior mitral leaflet and alcohol septal ablation. The successful implementation of the kissing balloon technique in this case underscores its potential to improve outcomes in LVOT obstruction.

Non-Canonical TERT Activity Initiates Osteogenesis in Calcific Aortic Valve Disease.

Calcific aortic valve disease is the pathological remodeling of valve leaflets. The initial steps in valve leaflet osteogenic reprogramming are not fully understood. As TERT (telomerase reverse transcriptase) overexpression primes mesenchymal stem cells to differentiate into osteoblasts, we investigated whether TERT contributes to the osteogenic reprogramming of valve interstitial cells. Human control and calcific aortic valve disease aortic valve leaflets and patient-specific human aortic valve interstitial cells were used in in vivo and in vitro calcification assays. Loss of function experiments in human aortic valve interstitial cells and cells isolated from Tert-/- and Terc-/- mice were used for mechanistic studies. Calcification was assessed in Tert+/+ and Tert-/- mice ex vivo and in vivo. In silico modeling, proximity ligation, and coimmunoprecipitation assays defined novel TERT interacting partners. Chromatin immunoprecipitation and cleavage under targets and tagmentation sequencing defined protein-DNA interactions. TERT protein was highly expressed in calcified valve leaflets without changes in telomere length, DNA damage, or senescence markers, and these features were retained in isolated primary human aortic valve interstitial cells. TERT expression increased with osteogenic or inflammatory stimuli, and knockdown or genetic deletion of TERT prevented calcification in vitro and in vivo. Mechanistically, TERT was upregulated via NF-κB and required to initiate osteogenic reprogramming, independent of its canonical reverse transcriptase activity and the long noncoding RNA TERC. TERT exerts noncanonical osteogenic functions via binding with STAT5 (signal transducer and activator of transcription 5). Depletion or inhibition of STAT5 prevented calcification. STAT5 was found to bind the promoter region of RUNX2 (runt-related transcription factor 2), the master regulator of osteogenic reprogramming. Finally, we demonstrate that TERT and STAT5 are upregulated and colocalized in calcific aortic valve disease tissue compared with control tissue. TERT's noncanonical activity is required to initiate calcification. TERT is upregulated via inflammatory signaling pathways and partners with STAT5 to bind the RUNX2 gene promoter. These data identify a novel mechanism and potential therapeutic target to decrease vascular calcification.

Effects of aortic valve calcification on transcatheter aortic valve replacement for low-flow, low-gradient aortic stenosis.

Patients with low-flow, low-gradient (LFLG) aortic stenosis (AS) have precarious hemodynamics and are a fragile population for intervention. Quantification of aortic valve calcification (AVC) severity is a critical component of the evaluation for transcatheter aortic valve replacement (TAVR); this study aims to further clarify its utility for risk stratification in LFLG AS. This retrospective study evaluated 467 patients with LFLG AS undergoing TAVR at a large quaternary-care hospital from January 2019 to December 2021. AVC was quantified with Agatston scores using pre-operative computed tomography angiograms. Primary endpoint was a composite of all-cause mortality and heart failure rehospitalization rates. 51 patients (10.9%) had mild calcification, 137 (29.3%) had moderate, and 279 (59.7%) had severe. Increased AVC severity correlated with increased AS severity by aortic valve area (0.69cm2 for mild AVC vs. 0.63cm2 for severe; p≤0.001), peak velocity (3.1m/s vs. 3.9m/s; p≤0.001), and mean gradient (21mmHg vs. 36mmHg; p≤0.001). Kaplan-Meier analysis showed increased reductions in the primary composite endpoint (p=0.023) and heart failure rehospitalization rates (p=0.005) for patients with greater AVC severity undergoing TAVR. Multivariate adjustments confirmed a significant reduction in heart failure rehospitalizations when comparing TAVR outcomes between mild and severe AVC (HR 0.40, 95% CI 0.18-0.91; p=0.028). Between the 3 groups, there were no significant differences in adjusted rates of paravalvular leak or other periprocedural complications. Increased AVC in LFLG AS does not correlate clinically with more severe AS by echocardiography. Patients with more severe AVC have less heart failure rehospitalizations and derive greater benefit from TAVR.

Association of aortic valve size with the degree of aortic valve calcification in severe high-gradient aortic stenosis.

Less pronounced calcification of the aortic valve (AVC) was observed in women with aortic stenosis (AS) as compared to men. Since women have smaller aortic valves (AV), this could explain a lower calcium load. We aimed to analyze the association of AV size with AVC independent from sex. Consecutive patients with high-gradient AS, who underwent cardiac computed tomography (CT), were assessed. AV annulus area and AVC with the Agatston score were measured on CT. In total, 601 patients (mean age 80±7 years, 45% female) were included. Women had smaller AV annulus areas (4.12±0.67cm2 vs 5.15 ±0.78cm2, p<0.001) and lower Agatston scores (2018 [1456-3017] vs. 3394 [2562-4530]; p<0.001) than men. We found a significant correlation (r=0.594, p<0.001) and independent association (β=926.20, p<0.001) of AV annulus area with AVC. On separate regression analyses for men and women, AVC was independently associated with AV annulus area in both sexes (βmen=887.77; βwomen=863.48, both p<0.001). When patients were stratified into AV size quartiles, patients in the lower quartiles were more likely to have AVC values below recommended sex-specific AVC thresholds. In the lowest quartile 28% of female and 27% of male patients had Agatston scores below 1200AU (women) and 2000AU (men) while this proportion decreased to 6% and 2%, respectively, in the quartiles with the largest annulus areas. In high-gradient AS, AVC strongly depends on AV annulus area. This association is not dependent on sex. Thus, AVC should be indexed to AV size in addition to sex.

Evaluating the Impacts of Procedural and Patient-Specific Factors on the Outcomes of Transcatheter Aortic Valve Implantation (TAVI).

Background: Transcatheter aortic valve implantation (TAVI) has emerged as a pivotal intervention for managing severe aortic stenosis in high-risk surgical patients. Objective: This study aimed to evaluate the impacts of procedural factors and patient characteristics on TAVI outcomes, with a focus on survival rates, cardiac mortality, and associated complications. Methods: A retrospective, single-center study involving 224 patients who underwent TAVI at the Lithuanian University of Health Sciences from September 2021 to April 2023 was conducted. Data encompassing demographic characteristics, medical history, procedural specifics, and follow-up outcomes were analyzed. Survival and adverse events were assessed at 30 days, 6 months, and 12 months post-TAVI. Results: The study included 224 patients. The mean age in the non-death group was 80 ± 6.17 years (range, 49-91), while that in the cardiac death group was 81.5 ± 6.14 years (range, 70-94; p = 0.079). Males accounted for 37.7% of the non-death group and 50% of the cardiac death group (p = 0.304). Statistical analyses identified factors significantly associated with mortality and complications. The overall survival rate was 88.8%, with cardiac-related mortality observed in 8% of patients. Increased fluoroscopy time (p < 0.001), a higher contrast volume (p = 0.005), and less improvement in aortic valve velocity post-TAVI (p = 0.031) were significantly associated with cardiac mortality. Advanced age and a reduced left ventricular ejection fraction (<50%) were prominent predictors of adverse outcomes. Patients with non-coronary cusp calcification exhibited lower cardiac mortality (p = 0.005), while mitral valve regurgitation was linked to poorer outcomes (p = 0.015). Logistic regression analysis underscored the incremental risks posed by procedural complexities and comorbidities. Conclusions: Procedural factors such as fluoroscopy duration and contrast volume, along with patient-specific attributes including age, left ventricular function, and valve calcification patterns, critically influence TAVI outcomes. These findings emphasize the need for tailored procedural strategies and patient management protocols to mitigate risks and enhance the efficacy of TAVI interventions.

Usefulness of Aortic Valve Calcification in Patients With Low-Flow Aortic Stenosis.

Aortic valve calcification (AVC) has been shown to be a powerful assessment of aortic stenosis (AS) severity and a predictor of adverse outcomes. However, its accuracy in patients with low-flow AS has not yet been proven. The objective of the study was to assess the predictive value of AVC in patients with classical low-flow (CLF, that is, low-flow reduced left ventricular ejection fraction) or paradoxical low-flow (PLF, that is, low-flow preserved left ventricular ejection fraction) AS. We prospectively included 641 patients, 319 (49.8%) with CLF-AS and 322 (50.2%) with PLF-AS, who underwent Doppler echocardiography and multidetector computed tomography. AVC ratio (AVCratio) was calculated as AVC divided by the sex-specific AVC threshold for AS severity; AVC score ≥2000 Agatston units in male patients and ≥1200 Agatston units in female patients. The primary end point of the study was all-cause mortality regardless of treatment. Sex-specific AVC thresholds identified AS severity correctly in 137 (87%) of the patients. During a median follow-up of 4.9 (4.3-5.9) years, there were 265 deaths. After comprehensive adjustment, AVCratio was associated with all-cause mortality in patients with CLF-AS (adjusted hazard ratio, 1.25 [95% CI, 1.01-1.56]; P=0.046) and PLF-AS (adjusted hazard ratio, 1.51 [95% CI, 1.14-2.00]; P=0.004). There was an interaction (P=0.001) between AVC and AS flow patterns (ie, CLF versus PLF) with regard to the prediction of mortality. The best AVCratio threshold to predict mortality was different in patients with CLF-AS (AVCratio ≥0.7) and PLF-AS (AVCratio ≥1). After a comprehensive analysis, AVCratio as a dichotomic variable was associated with all-cause mortality in all groups (P≤0.001). The addition of AVCratio to the models improved all models' predictive value (all net reclassification index >18%; all P≤0.05). In patients with CLF-AS or PLF-AS, AVC is a major predictor of mortality. Thus, AVC should be used in low-flow patients to assess AS severity and stratify risk. Importantly, in patients with reduced left ventricular ejection fraction, a nonsevere AS (ie, AVC 70% of severe) could be associated with reduced survival.

Frailty in Older Adults with Severe Aortic Stenosis: The Role of Systemic Inflammation and Calcium Homeostasis.

Background: Frailty and severe aortic stenosis (AoS) are critical conditions in older adults, both of which share pathophysiological mechanisms including chronic inflammation and calcium metabolism dysregulation, potentially influencing the development and progression of these conditions. This study aimed to analyze systemic inflammation and calcium homeostasis biomarkers and their associations with frailty in older adults with severe AoS. Methods: This prospective study included 191 patients aged ≥75 years with severe AoS who were candidates for aortic valve replacement and were evaluated at a Geriatrics Frailty Assessment and Intervention Clinic. Frailty was defined as a score ≤6 on the Short Physical Performance Battery (SPPB). Biomarkers analyzed included aortic valve calcium score, parathyroid hormone (PTH), calcidiol (vitamin D), calcium, phosphate, creatinine, interleukin-6 (IL-6), and the Systemic Immune-Inflammation Index. Multivariate logistic regression was performed to identify independent predictors of frailty. Results: Of the 191 patients studied, 53.9% were women, with a mean age of 84.1 ± 4.1 years. Frailty was identified in 28.3% of patients (mean SPPB score 7.6 ± 2.5). Statistically significant differences between frail and non-frail patients were observed for PTH (87.7 ± 61.1 pg/mL vs. 70 ± 44.4 pg/mL, p = 0.028) and IL-6 (10.4 ± 11.2 pg/mL vs. 7 ± 8.2 pg/mL, p = 0.049). Notably, in the multivariate model, IL-6 emerged as a significant independent predictor of frailty (OR 1.037; CI 1.001-1.074, p = 0.043). Conclusions: IL-6 was identified as a biomarker significantly associated with frailty in older adults with severe AoS. Evaluating IL-6 could enhance the precision of frailty assessments, complement functional measures, and support clinical decision-making in this population.

MARCH5 ameliorates aortic valve calcification via RACGAP1-DRP1 pathway associated mitochondrial quality control.

Mitochondrial E3 ubiquitin ligase (MARCH5) as an important regulator in maintaining mitochondrial function. Our aims were to investigate the role and mechanism of MARCH5 in aortic valve calcification. Human aortic valves, both calcified and non-calcified, were analyzed for MARCH5 expression using western blot. Mitochondrial fragmentation was observed under transmission electron microscope. Osteogenic differentiation of human aortic valvular interstitial cells (HVICs) was induced with osteoblastic medium (OM), confirmed by western blot and Alizarin red staining. Mitochondrial morphology and oxidative phosphorylation were assessed using MitoTracker and Seahorse, respectively. MARCH5-knockdown and ApoE-knockout mice fed high-fat diet were used to study aortic valve calcification. The mitochondrial quality control was impaired in calcified valves, and the level of MARCH5 protein was also decreased in calcified valves. Inhibition of MARCH5 impaired mitochondrial quality control, increased mitochondrial stress and accelerates osteogenic transformation in OM treated HVICs. While, overexpression MARCH5 has the opposite effects. Co-immunoprecipitation, mass spectrometry and molecular docking found MARCH5 interacted Rac GTPase-activating protein 1 (RACGAP1) and promoted its ubiquitination, leading to impaired mitochondrial quality control. Inhibiting RACGAP1 reversed osteogenic transformation induced by MARCH5 silencing in OM treated HVICs. Silencing dynamin-related protein 1 (DRP1) under RACGAP1 inhibition had no additional benefit. In vivo, deficiency of MARCH5 promoted aortic valve calcification, while inhibition RACGAP1 reversed aortic valve calcification in MARCH5 deficiency mice. Downregulation of MARCH5 promotes RACGAP1 ubiquitination, activating DRP1 and impairing mitochondrial quality control, which contributes to aortic valve calcification. This identifies a potential therapeutic target for aortic valve calcification.

Definitive diagnosis by cardiac MRI in caseous calcification of mitral valve

Definitive diagnosis by cardiac MRI in caseous calcification of mitral valve

Mid-life physical activity and calcification of coronary arteries, aorta, and cardiac valves in late life: the Atherosclerosis Risk in Communities (ARIC) Study

Mid-life physical activity and calcification of coronary arteries, aorta, and cardiac valves in late life: the Atherosclerosis Risk in Communities (ARIC) Study

A collagen-based laboratory model to mimic sex-specific features of calcific aortic valve disease.

Calcific aortic valve disease (CAVD) shows in the deposition of calcium phosphates in the collagen-rich layer of the valve leaflets. This stiffens the leaflets and eventually leads to heart failure. Recent research suggests that CAVD follows sex-specific pathways: at the same severity of the disease, women tend to have fewer and less crystalline calcifications, and the phases of their calcifications are decidedly different than those of men; namely, dicalcium phosphate dihydrate (DCPD) - one of the mineral phases in CAVD - occurs almost exclusively in females. Furthermore, the morphologies of heart valve calcifications might be sex specific, but the sex-dependence of the morphologies has not been systematically investigated. Herein, we first show that male CAVD patients have more compact and less fibrous calcifications than females, establishing sex-dependent morphological features of heart valve calcification. We then build a model that recapitulates the sex differences of the calcifications in CAVD, which is based on a collagen gel that we calcify in simulated body fluid with varying fetuin A concentrations. With increasing fetuin A concentration, the calcifications become less crystalline and more fibrous, and more DCPD deposits in the collagen matrix, resembling the physicochemical characteristics of the calcifications in female valves. Lower fetuin A concentrations give rise to a model that replicates male-specific mineral characteristics. The models could be used to develop sex-specific detection and treatment methods for CAVD. STATEMENT OF SIGNIFICANCE: Although calcific aortic valve disease (CAVD) affects ∼10 million people globally, researchers have only discovered recently that the disease follows sex-specific pathways, and many of its sex-specific features remain unknown. To further our understanding of sex differences in CAVD and to develop better detection and treatment methods, there is an urgent need to establish models for CAVD that account for its sex-specific manifestations. In this study, we first show that CAVD calcifications in men and women take on different morphologies. Second, we present a model that can replicate physicochemical calcification characteristics of male or female valves, including morphology, and that can help to develop sex-specific detection and treatment methods for CAVD.

Impact of Early Menopause and Hormonal Therapy Replacement on Aortic Stenosis Progression.

Early menopause has been associated with several cardiovascular diseases. Its impact on the progression of aortic stenosis (AS) remains unknown. We conducted an analysis to examine the impact of early menopause without hormonal replacement therapy (HRT) on the progression of AS in postmenopausal women with AS. This sub-analysis included 33 female patients with at least mild AS (mean age 65±10) prospectively enrolled in the PROGRESSA study (NCT01679431). Anatomical assessment of AS was performed by multidetector computed tomography, while hemodynamic assessment of AS was performed by Doppler-echocardiography. Over a median follow-up of 2[1-4] years, early menopausal women without HRT showed faster progression of aortic valve calcification (AVC) (100[58-130] vs. 23[2-71] AU/year, p=0.03, mean pressure gradient (MG) 2.37[0.82-3.61] vs. 0.33[0.01-1.78] mmHg/year, p=0.04, and aortic valve area indexed to body surface area (AVAi) (-0.12[-0.23;0.002] vs. -0.004[-0.07;0.08] cm2/m2/year, p=0.07). In multivariate analysis adjusted for several clinical, echocardiographic and anatomic factors, early menopause without HRT remained independently associated with faster AVC progression (p=0.003). Women who received HRT showed a slower progression of AVC compared with those who never received HRT (62[2-100] vs. (20[10-42] AU/year, p=0.13). Multivariate analysis also showed that AVC progressed less rapidly in women who received HRT (p=0.04). In this study of post-menopausal women with AS, early menopause without HRT was associated with faster progression of AS, both anatomically and hemodynamically. However, the use of HRT was associated with slower progression of AS.

Reevaluating Normal-Flow Low-Gradient Severe Aortic Stenosis: Clinical Phenotypes and Outcomes in Severe Aortic Stenosis Among TAVR Patients.

Aortic stenosis (AS) is a complex condition with various hemodynamic subtypes, each with distinct clinical profiles and outcomes. This study aimed to assess the characteristics and outcomes of different AS phenotypes based on flow and gradient patterns. In this retrospective cohort study, we included 930 patients who underwent transcatheter aortic valve replacement (TAVR) for severe symptomatic AS at Mayo Clinic sites from 2012-2017. Patients were classified into three groups: high gradient (HG), low-flow low-gradient (LFLG), and normal-flow low-gradient (NFLG). Baseline clinical, echocardiographic, and computed tomography (CT) characteristics, including aortic valve area (AVA), aortic valve calcium score (AVCS), left ventricular ejection fraction (LVEF), and the prevalence of tricuspid regurgitation (TR) and atrial fibrillation were analyzed. One- and five-year all-cause mortality outcomes were compared using Kaplan-Meier analysis and Cox proportional hazards models. The final cohort included 273 patients in the NFLG group (29.4%), 563 in the HG group (60.5%), and 94 in the LFLG group (10.1%). After reevaluation and careful review of the echocardiograms, 41 NFLG patients were reclassified into the LFLG group. LFLG patients had the highest prevalence of atrial fibrillation/flutter (60%) and TR (17%). AVCS was significantly lower in NFLG compared to HG and LFLG groups. One-year mortality was highest in the LFLG group (17.4%), followed by HG (13.9%) and NFLG (10.9%), but the difference was not statistically significant (p=0.2). Five-year mortality rate was higher in the LFLG group (55.6%) compared to NFLG (47.2%) and HG (47.9%) but did not reach statistical significance (p=0.2). LFLG AS is associated with more comorbidities and higher mortality compared to HG and NFLG groups, though differences in mortality were not statistically significant. The NFLG group, after close review and reclassification, showed the least significant AS. Randomized trials are needed to clarify the prognosis and management of NFLG AS.

Can aortic valve calcium score predict a need for permanent pacemaker implantation after transcatheter aortic valve implantation?

IntroductionConductive disturbances requiring permanent pacemaker (PPM) implantation remain a major concern after transcatheter aortic valve implantation (TAVI).AimsTo assess the impact of aortic valve calcium score (AVCS) on conductive disturbances requiring...

Optimizing Outcomes in Transcatheter Aortic Valve Replacement Addressing Cerebrovascular Complications and Enhancing Patient Safety.

Transcatheter aortic valve replacement (TAVR) has revolutionized the treatment of severe aortic stenosis, becoming the gold standard for many patients. Despite its advantages over surgical aortic valve replacement, TAVR is associated with significant complications, including paravalvular leakage, conduction disorders, and cerebrovascular events. This review focuses on the pathophysiology, incidence, and management of cerebrovascular complications following TAVR. We explore the mechanisms leading to these events, including embolization of debris from the calcified valve and aortic arch, and the role of procedural factors. The review also discusses the timing of cerebrovascular events, diagnostic approaches, and potential preventive strategies, including embolic protection devices. Understanding these complications is crucial for improving patient outcomes and refining TAVR techniques.

Impact of Wood Smoke Exposure on Aortic Valve Mineralization: Microvesicles as Mineral Conveyors in Patients with Coronary Stenosis.

Background: Aortic valve calcification results from degenerative processes associated with several pathologies. These processes are influenced by age, chronic inflammation, and high concentrations of phosphate ions in the plasma, which contribute to induce mineralization in the aortic valve and deterioration of cardiovascular health. Environmental factors, such as wood smoke that emits harmful and carcinogenic pollutants, carbon monoxide (CO), and nitrogen oxide (NOx), as well as other reactive compounds may also be implicated. The purpose of this research was to study the impact of wood smoke on specific aortic valve characteristics, including lesion size and percentage of mineralization, in patients with aortic valve stenosis (AS). Methods: This observational study included 65 patients who underwent primary valve replacement surgery at the National Institute of Cardiology, 11 of whom were exposed to wood smoke. For each patient, approximately 0.5 cm of aortic valve tissue was collected along with a blood sample anticoagulated with sodium citrate. The valves were analyzed using scanning electron microscopy coupled with energy-dispersive X-ray spectroscopy (SEM-EDS). Since extracellular microvesicles (MVs) may induce epigenetic changes in target cells by transferring their cargo, we also analyzed their mineral content. Results: Individuals exposed to wood smoke exhibit more extensive lesion (835 µm2) characteristics compared to those with no exposure (407.5 µm2). Interestingly, FESEM images of MVs showed the presence of minerals on their surface, thus providing evidence on their possible role in the pathophysiology of mineralization. Conclusions: Our study uniquely demonstrates imaging-based evidence of structural damage and mineralization in aortic valve tissue, with chronic wood smoke exposure emerging as a significant causative factor.

Iron Deficiency Promotes Intra-leaflet Haemorrhage-induced Aortic Valve Calcification: an Experimental Study.

Interleaflet haemorrhage (IH) plays a well-recognized detrimental role in calcified aortic valve disease (CAVD). However, IH-induced fibro-osteogenic responses in valvular interstitial cells (VICs) appear to be triggered under specific pathological conditions. Iron deficiency (ID), a common co-morbidity in CAVD, may influence these responses. This study investigated the relationship between ID and pathological changes associated with CAVD, and its effects on IH-mediated fibro-osteogenic differentiation of VICs. Two independent studies were conducted, including 2,495 patients in the discovery study and 34 in the validation study. Our data demonstrated that ID was associated with CAVD severity and progression, particularly in an age-dependent manner. Based on these clinical findings, immunofluorescence and Western blot analyses revealed that TFR1, a key iron import transporter, was significantly upregulated in human calcified aortic valves. Concurrently, iron accumulation was detected by Perl's staining in both calcific and non-calcific valve sections. In vitro, VICs cultured with human serum from ID patients showed red blood cell lysis-induced iron overload and fibro-calcific differentiation. ID triggers TFR1-mediated intracellular iron overload, leading to fibrosis and calcification in human VICs, thereby contributing to IH-mediated valve remodeling and calcification. These findings supported the potential role of monitoring and correcting ID to slow or prevent the progression of valvular calcification.