Search Results (51)

Objectives: CT-derived fractional flow reserve (CT-FFR) can improve the specificity of coronary CT-angiography (cCTA) for ruling out relevant coronary artery disease (CAD) prior to transcatheter aortic valve replacement (TAVR). However, little is known about the reproducibility of CT-FFR and the influence of diffuse coronary artery calcifications or segment location. The objective was to assess the reliability of machine-learning (ML)-based CT-FFR prior to TAVR in patients without obstructive CAD and to assess the influence of image quality, coronary artery calcium score (CAC), and the location of measurement within the coronary tree. Methods: Patients assessed for TAVR, without obstructive CAD on cCTA were evaluated with ML-based CT-FFR by two observers with differing experience. Differences in absolute values and categorization into hemodynamically relevant CAD (CT-FFR ≤ 0.80) were compared. Results in regard to CAD were also compared against invasive coronary angiography. The influence of segment location, image quality, and CAC was evaluated. Results: Of the screened patients, 109/388 patients did not have obstructive CAD on cCTA and were included. The median (interquartile range) difference of CT-FFR values was −0.005 (−0.09 to 0.04) (p = 0.47). Differences were smaller with high values. Recategorizations were more frequent in distal segments. Diagnostic accuracy of CT-FFR between both observers was comparable (proximal: Δ0.2%; distal: Δ0.5%) but was lower in distal segments (proximal: 98.9%/99.1%; distal: 81.1%/81.6%). Image quality and CAC had no clinically relevant influence on CT-FFR. Conclusions: ML-based CT-FFR evaluation of proximal segments was more reliable. Distal segments with CT-FFR values close to the given threshold were prone to recategorization, even if absolute differences between observers were minimal and independent of image quality or CAC. Full article

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. Full article

Background/Objectives: The aim of this study was to analyze a group of patients with a bicuspid aortic valve (BAV) examined with ECG-gated cardiac CT (ECG-CT), focusing on the assessment of the clinical reasons for cardiac CT, cardiovascular abnormalities coexisting with their BAV, and coronary artery stenosis. Methods: A detailed statistical analysis was conducted on 700 patients with a BAV from a group of 15,670 patients examined with ECG-CT. Results: The incidence of a BAV in ECG-CT was 4.6%. The most common reason for examination was suspicion of coronary heart disease—31.1%. Cardiovascular defects most frequently associated with a BAV were a VSD (4.3%) and coarctation of the aorta (3.6%), while among coronary anomalies, they were high-take-off coronary arteries (6.4%) and paracommissural orifice of coronary arteries (4.4%). The analysis of the coronary artery calcium index showed significantly lower values for type 2 BAV compared to other valve types (p < 0.001), with the lowest average age in this group of patients. Moreover, the presence of a raphe between the coronary and non-coronary cusps was associated with a higher rate of significant coronary stenosis compared to other types of BAVs (p < 0.001). Conclusions: The most common reason for referral for cardiac ECG-CT in the group ≤ 40-year-olds with a BAV was the suspicion of congenital cardiovascular defects, while in the group of over 40-year-olds, it was the suspicion of coronary artery disease. The incidence of cardiovascular abnormalities co-occurring with BAV and diagnosed with ECG-CT differs among specific patient subgroups. The presence of a raphe between the coronary and non-coronary cusps appears to be a potential risk factor for significant coronary stenosis in patients with BAVs. Full article

Rest and stress echocardiography (SE) play a fundamental role in the evaluation of aortic valve stenosis (AS). According to the current guidelines for the echocardiographic evaluation of patients with aortic stenosis, four broad categories can be defined: high-gradient AS (mean gradient ≥ 40 mmHg, peak velocity ≥ 4 m/s, aortic valve area (AVA) ≤ 1 cm² or indexed AVA ≤ 0.6 cm²/m²); low-flow, low-gradient AS with reduced ejection fraction (mean gradient < 40 mmHg, AVA ≤ 1 cm², left ventricle ejection fraction (LVEF) < 50%, stroke volume index (Svi) ≤ 35 mL/m²); low-flow, low-gradient AS with preserved ejection fraction (mean gradient < 40 mmHg, AVA ≤ 1 cm², LVEF ≥ 50%, SVi ≤ 35 mL/m²); and normal-flow, low-gradient AS with preserved ejection fraction (mean gradient < 40 mmHg, AVA ≤ 1 cm², indexed AVA ≤ 0.6 cm²/m², LVEF ≥ 50%, SVi > 35 mL/m²). Aortic valve replacement (AVR) is indicated with the onset of symptoms development or LVEF reduction. However, there is often mismatch between resting transthoracic echocardiography findings and patient’s symptoms. In these discordant cases, SE and CT calcium scoring are among the indicated methods to guide the management decision making. Additionally, due to the increasing evidence that in asymptomatic severe aortic stenosis an early AVR instead of conservative treatment is associated with better outcomes, SE can help identify those that would benefit from an early AVR by revealing markers of poor prognosis. Low-flow, low-gradient AS represents a challenge both in diagnosis and in therapeutic management. Low-dose dobutamine SE is the recommended method to distinguish true-severe from pseudo-severe stenosis and assess the existence of flow (contractile) reserve to appropriately guide the need for intervention in these patients. Full article

Background/Objectives: Among patients with suspected severe aortic stenosis (AS), discordance between effective orifice area (EOA) and transvalvular gradients is frequent and requires a multiparametric workup including flow assessment and calcium-scoring to confirm true severe AS. The aim of this study was to assess direct planimetry, energy loss index (Eli) and dimensionless index (DI) as stand-alone parameters to identify non-severe AS in discordant cases. Methods: In this prospective cohort study, we included consecutive AS patients > 70 years with EOA < 1.0 cm² referred for valve replacement between 2014 and 2017. AS severity was retrospectively reassessed using the multiparametric work-up recommended in the 2021 ESC/EACTS guidelines. DI and ELi were calculated, and valve area was measured by direct planimetry on transesophageal echocardiography. Results: A total of 101 patients (mean age 82 y; 57% male) were included. Discordance between EOA and gradients was observed in 46% and non-severe AS found in 24% despite an EOA < 1 cm². Valve planimetry performed poorly, with an area under the ROC curve (AUC) of 0.64. At a cut-off value of >0.82 cm², sensitivity and specificity to identify non-severe AS were 67 and 66%, respectively. DI and ELi showed a higher diagnostic accuracy, with an AUC of 0.77 and 0.76, respectively. Cut-off values of >0.24 and >0.6 cm²/m² identified non-severe AS, with a high specificity of 79% and 91%, respectively. Conclusions: Almost one in four patients with EOA < 1 cm² had non-severe AS according to guideline-recommended multiparametric assessment. Direct valve planimetry revealed poor diagnostic accuracy and should be interpreted with caution. Usual prognostic cut-off values for DI > 0.24 and ELI > 0.6 cm²/m² identified non-severe AS with high specificity and should therefore be included in the assessment of low-gradient AS. Full article

Background: The goal of our study is to evaluate a method to quantify aortic valve calcification (AVC) in contrast-enhanced computed tomography for patients with suspected severe aortic stenosis pre-interventionally. Methods: A total of sixty-five patients with aortic stenosis underwent both a native and a contrast-enhanced computed tomography (CECT) scan of the aortic valve (45 in the training cohort and 20 in the validation cohort) using a standardized protocol. Aortic valve calcification was semi-automatically quantified via the Agatston score method for the native scans and was used as a reference. For contrast-enhanced computed tomography, a calcium threshold of the Hounsfield units of the aorta plus four times the standard deviation was used. Results: For the quantification of aortic valve calcification in contrast-enhanced computed tomography, a conversion formula (691 + 1.83 x AVCCECT) was derived via a linear regression model in the training cohort. The validation in the second cohort showed high agreement for this conversion formula with no significant proportional bias (Bland–Altman, p = 0.055) and with an intraclass correlation coefficient in the validation cohort of 0.915 (confidence interval 95% 0.786–0.966) p < 0.001. Conclusions: Calcium scoring in patients with aortic valve stenosis can be performed using contrast-enhanced computed tomography with high validity. Using a conversion factor led to an excellent agreement, thereby obviating an additional native computed tomography scan. This might contribute to a decrease in radiation exposure. Full article

Background: There is emerging but conflicting evidence regarding the association between calcium biomarkers, more specifically ionized calcium and the prognosis of intensive care unit (ICU) postoperative cardiac patients. Methods: Our study investigated the relationship between ionized calcium, vitamin D, and periprocedural clinical events such as cardiac, neurologic and renal complications, major bleeding, vasoactive–inotropic score (VIS), and length of ICU and hospitalization. Results: Our study included 83 consecutive subjects undergoing elective major cardiac surgery requiring cardiopulmonary bypass. The mean age of the participants was 64.9 ± 8.5 years. The majority of procedures comprised isolated CABG (N = 26, 31.3%), aortic valve procedures (N = 26, 31.3%), and mitral valve procedures (N = 12, 14.5%). A difference in calcium levels across all time points (p < 0.001) was observed, with preoperative calcium being directly associated with intraoperative VIS (r = 0.26, p = 0.016). On day 1, calcium levels were inversely associated with the duration of mechanical ventilation (r = −0.30, p = 0.007) and the length of hospital stay (r = −0.22, p = 0.049). At discharge, calcium was inversely associated with length of hospital stay (r = −0.22, p = 0.044). All calcium levels tended to be lower in those who died during the 1-year follow-up (p = 0.054). Preoperative vitamin D levels were significantly higher in those who experienced AKI during hospitalization (median 17.5, IQR 14.5–17.7, versus median 15.3, IQR 15.6–20.5, p = 0.048) Conclusion: Fluctuations in calcium levels and vitamin D may be associated with the clinical course of patients undergoing cardiac surgery. In our study, hypocalcemic patients exhibited a greater severity of illness, as evidenced by elevated VIS scores, and experienced prolonged mechanical ventilation time and hospital stays. Additional larger-scale studies are required to gain a deeper understanding of their impact on cardiac performance and the process of weaning from cardiopulmonary bypass, as well as to distinguish between causal and associative relationships. Full article

Calcification is a process of accumulation of calcium in tissues and deposition of calcium salts by the crystallization of PO₄³⁻ and ionized calcium (Ca²⁺). It is a crucial process in the development of bones and teeth. However, pathological calcification can occur in almost any soft tissue of the organism. The better studied is vascular calcification, where calcium salts can accumulate in the intima or medial layer or in aortic valves, and it is associated with higher mortality and cardiovascular events, including myocardial infarction, stroke, aortic and peripheral artery disease (PAD), and diabetes or chronic kidney disease (CKD), among others. The process involves an intricate interplay of different cellular components, endothelial cells (ECs), vascular smooth muscle cells (VSMCs), fibroblasts, and pericytes, concurrent with the activation of several signaling pathways, calcium, Wnt, BMP/Smad, and Notch, and the regulation by different molecular mediators, growth factors (GFs), osteogenic factors and matrix vesicles (MVs). In the present review, we aim to explore the cellular players, molecular pathways, biomarkers, and clinical treatment strategies associated with vascular calcification to provide a current and comprehensive overview of the topic. Full article

Calcific aortic valve disease (CAVD) is the most common heart valve disease among aging populations. There are two reported pathways of CAVD: osteogenic and dystrophic, the latter being more prevalent. Current two-dimensional (2D) in vitro CAVD models have shed light on the disease but lack three-dimensional (3D) cell–ECM interactions, and current 3D models require osteogenic media to induce calcification. The goal of this work is to develop a 3D dystrophic calcification model. We hypothesize that, as with 2D cell-based CAVD models, programmed cell death (apoptosis) is integral to calcification. We model the cell aggregation observed in CAVD by creating porcine valvular interstitial cell spheroids in agarose microwells. Upon culture in complete growth media (DMEM with serum), calcium nodules form in the spheroids within a few days. Inhibiting apoptosis with Z-VAD significantly reduced calcification, indicating that the calcification observed in this model is dystrophic rather than osteogenic. To determine the relative roles of oxidative stress and extracellular matrix (ECM) production in the induction of apoptosis and subsequent calcification, the media was supplemented with antioxidants with differing effects on ECM formation (ascorbic acid (AA), Trolox, or Methionine). All three antioxidants significantly reduced calcification as measured by Von Kossa staining, with the percentages of calcification per area of AA, Trolox, Methionine, and the non-antioxidant-treated control on day 7 equaling 0.17%, 2.5%, 6.0%, and 7.7%, respectively. As ZVAD and AA almost entirely inhibit calcification, apoptosis does not appear to be caused by a lack of diffusion of oxygen and metabolites within the small spheroids. Further, the observation that AA treatment reduces calcification significantly more than the other antioxidants indicates that the ECM stimulatory effect of AA plays a role inhibiting apoptosis and calcification in the spheroids. We conclude that, in this 3D in vitro model, both oxidative stress and ECM production play crucial roles in dystrophic calcification and may be viable therapeutic targets for preventing CAVD. Full article

Background and aim: Tools that assist interventionists in selecting patients for post-dilation (PD) are needed. We aimed to assess whether pre-interventional aortic valve calcium (AVC) or the peri-interventional aortic regurgitation (ARI) ratio is a better predictor for a more than mild paravalvular leak (PVL) requiring PD after TAVI. Methods: Patients undergoing TAVI with available data on AVC derived from MSCTs and the ARI ratio derived from peri-interventional hemodynamic curves were studied. The main outcome was moderate-to-severe PVL requiring PD. Results: In 237 patients, more than mild PVL after valve deployment was present in 25.7%. PD was performed in 65 patients. The median (IQR) total AVC was 390.5 (211.5–665.4) mm³. All calcification values were significantly higher in patients who underwent PD. The median (IQR) individual threshold was 600 (550–685) Hus. The overall ARI ratio was 0.78 (0.61–0.96), with values being significantly lower in patients who underwent PD: 0.61 (0.49–0.80) vs. 0.82 (0.69–0.99) (p < 0.001). Both the ARI ratio (OR [95%CI] 0.053 [0.014–0.203]; p < 0.001) and AVC (1.01 [1.000–1.002]; p = 0.015) predicted PD need. ROC curves showed higher discrimination for the ARI ratio (AUC 0.73) than for any calcification parameter (all AUCs ≤ 0.62). Conclusions: The ARI ratio provides interventionists with a powerful predictive tool for PVL requiring PD after TAVI that is beyond the predictive value of pre-procedural valve calcification derived from MSCT. Full article

Calcified aortic valve disease in its final stage leads to aortic valve stenosis, limiting cardiac function. To date, surgical intervention is the only option for treating calcific aortic valve stenosis. This study combined controlled drug delivery by nanoparticles (NPs) and active targeting by antibody conjugation. The chelating agent diethylenetriaminepentaacetic acid (DTPA) was covalently bound to human serum albumin (HSA)-based NP, and the NP surface was modified using conjugating antibodies (anti-elastin or isotype IgG control). Calcification was induced ex vivo in porcine aortic valves by preincubation in an osteogenic medium containing 2.5 mM sodium phosphate for five days. Valve calcifications mainly consisted of basic calcium phosphate crystals. Calcifications were effectively resolved by adding 1–5 mg DTPA/mL medium. Incubation with pure DTPA, however, was associated with a loss of cellular viability. Reversal of calcifications was also achieved with DTPA-coupled anti-elastin-targeted NPs containing 1 mg DTPA equivalent. The addition of these NPs to the conditioned media resulted in significant regression of the valve calcifications compared to that in the IgG-NP control without affecting cellular viability. These results represent a step further toward the development of targeted nanoparticular formulations to dissolve aortic valve calcifications. Full article

Aortic valve stenosis (AS) is increasing in prevalence due to the aging population, and severe AS is associated with significant morbidity and mortality. Echocardiography remains the mainstay for the initial detection and diagnosis of AS, as well as for grading of severity. However, there are important subgroups of patients, for example, patients with low-flow low-gradient or paradoxical low-gradient AS, where quantification of severity of AS is challenging by echocardiography and underestimation of severity may delay appropriate management and impart a worse prognosis. Aortic valve calcium score by computed tomography has emerged as a useful clinical diagnostic test that is complimentary to echocardiography, particularly in cases where there may be conflicting data or clinical uncertainty about the degree of AS. In these situations, aortic valve calcium scoring may help re-stratify grading of severity and, therefore, further direct clinical management. This review presents the evolution of aortic valve calcium score by computed tomography, its diagnostic and prognostic value, as well as its utility in clinical care. Full article

Introduction. The most common minimally invasive approach for aortic valve replacement (AVR) is the partial upper mini-sternotomy. The aim of this study is to understand which preoperative computed tomography (CT) features are predictive of longer operations in terms of cardio-pulmonary bypass timesand cross-clamp times. Methods. From 2011 to 2022, we retrospectively selected 246 patients which underwent isolated AVR and had a preoperative ECG-gated CT scan. On these patients, we analysed the baseline anthropometric characteristics and the following CT scan parameters: aortic annular dimensions, valve calcium score, ascending aorta length, ascending aorta inclination and aorta–sternum distance. Results. We identified augmented body surface area (>1.9 m²), augmented annular diameter (>23 mm), high calcium score (>2500 Agatson score) and increased aorta–sternum distance (>30 mm) as independent predictors of elongated operation times (more than two-fold). Conclusions. Identifying the preoperative predictive factors of longer operations can help surgeons select cases suitable for minimally invasive approaches, especially in a teaching context. Full article

Background: Calcific aortic valve disease (CAVD) is a significant cause of morbidity and mortality among elderly people. However, no effective medications have been approved to slow or prevent the progression of CAVD. Here, we examined the effect of liraglutide on aortic valve stenosis. Methods: Male Apoe^−/− mice were fed with a high-cholesterol diet for 24 weeks to generate an experimental CAVD model and randomly assigned to a liraglutide treatment group or control group. Echocardiography and immunohistological analyses were performed to examine the aortic valve function and morphology, fibrosis, and calcium deposition. Plasma Glucagon-like peptide-1 (GLP-1) levels and inflammatory contents were measured via ELISA, FACS, and immunofluorescence. RNA sequencing (RNA-seq) was used to identify liraglutide-affected pathways and processes. Results: Plasma GLP-1 levels were reduced in the CAVD model, and liraglutide treatment significantly improved aortic valve calcification and functions and attenuated inflammation. RNA-seq showed that liraglutide affects multiple myofibroblastic and osteogenic differentiations or inflammation-associated biological states or processes in the aortic valve. Those liraglutide-mediated beneficial effects were associated with increased GLP-1 receptor (GLP-1R) expression. Conclusions: Liraglutide blocks aortic valve calcification and may serve as a potential therapeutic drug for CAVD treatment. Full article

The bicuspid aortic valve (BAV) is the most common cardiovascular congenital abnormality and is frequently associated with proximal aortopathy. We analyzed the tissues of patients with bicuspid and tricuspid aortic valve (TAV) regarding the protein expression of the receptor for advanced glycation products (RAGE) and its ligands, the advanced glycation end products (AGE), as well as the S100 calcium-binding protein A6 (S100A6). Since S100A6 overexpression attenuates cardiomyocyte apoptosis, we investigated the diverse pathways of apoptosis and autophagic cell death in the human ascending aortic specimen of 57 and 49 patients with BAV and TAV morphology, respectively, to identify differences and explanations for the higher risk of patients with BAV for severe cardiovascular diseases. We found significantly increased levels of RAGE, AGE and S100A6 in the aortic tissue of bicuspid patients which may promote apoptosis via the upregulation of caspase-3 activity. Although increased caspase-3 activity was not detected in BAV patients, increased protein expression of the 48 kDa fragment of vimentin was detected. mTOR as a downstream protein of Akt was significantly higher in patients with BAV, whereas Bcl-2 was increased in patients with TAV, assuming a better protection against apoptosis. The autophagy-related proteins p62 and ERK1/2 were increased in patients with BAV, assuming that cells in bicuspid tissue are more likely to undergo apoptotic cell death leading to changes in the wall and finally to aortopathies. We provide first-hand evidence of increased apoptotic cell death in the aortic tissue of BAV patients which may thus provide an explanation for the increased risk of structural aortic wall deficiency possibly underlying aortic aneurysm formation or acute dissection. Full article