Search Results (55)

Background: Patients undergoing maintenance hemodialysis (HD) have a high risk of developing cardiovascular diseases due to calcification of the heart valves and coronary arteries, which results in a high mortality rate. In particular, aortic stenosis (AS) is an independent risk factor for heart failure-related mortality in patients undergoing HD. Recently, the analysis of digitized heart sounds using artificial intelligence (AI) has promoted the automation of cardiac disease detection and technological advances in diagnostic algorithms. Methods: We retrospectively investigated the 203 consecutive patients receiving HD who had undergone visualized phonocardiography using a regulatory-approved medical device (Japan) between January and May 2025 to detect AS. The usefulness of this phonocardiogram device, which utilizes acoustic analysis and an AI-based automatic diagnostic algorithm named the “Super Stethoscope”, was evaluated for the screening of AS in patients undergoing HD based on comparisons with findings obtained from echocardiography. Results: The results showed a significant correlation between the severity of systolic murmurs determined by the AI-based approach and the peak aortic jet velocity measured in 19 patients diagnosed with AS using transthoracic echocardiography (r = 0.578, p < 0.05). Additionally, for the AI-based diagnosis of AS based on systolic murmurs, the sensitivity and specificity in detecting moderate or severe AS were 0.90 and 0.70, respectively, among the patients undergoing HD. Conclusions: The AI-based diagnostic approach using the ECG-gated phonocardiogram “Super Stethoscope” could be a promising tool for AS screening. Transthoracic echocardiography is recommended in cases classified as grade B or higher by AI-based assessment. Full article

Background: Bicuspid aortic valve (BAV) is the most common congenital heart defect, and its complications (namely, dilatation of the thoracic ascending aorta) raise concerns regarding the proper timing of aortic surgery. The study aim is to unravel the genetic basis of BAV and its complications through a high-throughput sequencing (HTS) approach and segregation analysis if family members were available. Methods: Fifty-two Italian BAV patients were analyzed by HTS using the Illumina MiSeq platform. Targeted sequencing of 97 genes known to be or plausibly associated with connective tissue disorders or aorthopathy was performed. Thirty-five first-degree relatives of N = 10 probands underwent mutational screening for variants identified in the index cases. Results: HTS identified 194 rare (MAF < 0.01) variants in 63 genes. Regarding previously reported genes, five NOTCH1 variants in four BAV patients, four FBN1 variants in two patients and one GATA5 variant in one patient were identified. Interestingly, among further loci, the possible contribution of PDIA2, LRP1 and CAPN2 was suggested by (a) the increased prevalence of rare genetic variants, independently from their ACMG classification in the whole BAV cohort, and (b) segregation analyses of variants identified in family members. Moreover, the present data also suggest the possible contribution of rare variants to BAV complications, specifically MYLK in aortic dilatation, CAPN2 in BAV calcification and VHL and AGGF1 in valve stenosis. Conclusions: Our results underline clinical and genetic diagnosis complexity in traits considered monogenic, such as BAV, but characterized by variability in disease phenotypic expression (incomplete penetrance), as well as the contribution of different major and modifier genes to the development of complications. Full article

Aortic stenosis (AS) is a common degenerative valvular disease in elderly patients, causing obstruction of left ventricular outflow and presenting with symptoms such as angina, syncope, and heart failure. Although surgical aortic valve replacement (SAVR) remains the gold standard, its high perioperative risk in frail patients has led to the adoption of transcatheter aortic valve implantation (TAVI) as a less invasive and effective alternative. The transfemoral (TF) access route is generally preferred, but severe peripheral arterial disease may limit its feasibility. We report the case of a 71-year-old woman with critical AS complicated by multiple comorbidities, including extensive vascular calcifications, a porcelain aorta, and significant subrenal abdominal aortic stenosis. Multimodal imaging, including computed tomography, was essential for procedural planning, revealing complex iliofemoral anatomy unsuitable for conventional device passage without intervention. Intravascular lithotripsy (IVL) was used to disrupt calcific plaques and facilitate safe vascular access. The TAVI procedure was successfully performed under local anesthesia via TF access using a 65 cm GORE® DRYSEAL Flex Introducer Sheath (W. L. Gore & Associates, Flagstaff, AZ, USA) (18-Fr). After balloon valvuloplasty performed over a SAFARI2™ Pre-Shaped TAVI Guidewire, Extra Small (Boston Scientific, Marlborough, MA, USA) Curve in the left ventricle, a self-expanding Medtronic Evolut™ FX 26 (Medtronic, Minneapolis, MN, USA)mm transcatheter valve was implanted. Postoperative imaging confirmed optimal valve function and vascular integrity without complications. This case highlights the role of IVL as an innovative adjunctive technique enabling TF-TAVI in patients with challenging vascular anatomy, thereby expanding treatment options for high-risk individuals with severe AS. Full article

Calcific aortic valve disease (CAVD) is a prevalent cardiovascular condition and is the most common heart valve disease globally. Hyperlipidemia and aging are key risk factors; consequently, with the aging global population, CAVD incidence continues to rise. Despite extensive research, the pathogenesis of CAVD remains unclear, leading to a lack of effective pharmacological therapies. Consequently, valve replacement surgery persists as the primary treatment option. Establishing suitable animal models is crucial for investigating the complex pathophysiological mechanisms of CAVD in vivo, although an optimal model has yet to be identified. This review provides a concise overview of CAVD pathogenesis and summarizes the application of common animal models—including mice, rats, rabbits, and pigs—in studying valve calcification. We specifically detail the construction of various models and their associated calcific aortic valve phenotypes. Furthermore, we outline common detection methods for assessing aortic valve calcification in these models and suggest future directions for developing improved animal models relevant to CAVD research. Full article

The possible protective effect of obesity in the outcomes of chronic kidney disease (CKD) patients is an understudied field. We aimed to evaluate the prognostic value of vascular calcification (VC) on long-term outcomes in obese and non-obese CKD patients. We conducted a single-centre, prospective observational study of 150 CKD patients. Patients were divided into two groups using body mass index (BMI) scores (BMI ≥ 30 kg/m² and BMI < 30 kg/m²). Lateral lumbar X-rays (Kauppila score), the ankle–brachial index (ABI), and echocardiography were used for assessing VC. By the 11.2-year follow-up, 70 patients had died (47%). Twenty-four patients had had CV complications: stroke, myocardial infarction, decompensated heart failure, amputation caused by atherosclerosis, and aortic rupture. Among obese patients (BMI ≥ 30 kg/m²), only LVH was a significant predictor of CV complications (p = 0.01) and mortality (p = 0.004). In patients with BMI < 30 kg/m², predictors of CV complications and mortality were ABI (p = 0.03; p = 0.009), LVH (p = 0.02 for CV complications) and heart valve lesions (p = 0.009; p = 0.004). There were no differences in the measured parameters of VC between the obese and non-obese groups. Moreover, no significant differences were found comparing patients with and without obesity according to the studied parameters; we found no significant differences in complications and mortality. VC in patients with CKD is a significant complication that negatively impacts outcomes. Obesity does not have a protective effect in long-term outcomes in CKD patients. Full article

Calcific aortic stenosis (CAS) is a newly emerging pandemic in elderly individuals due to the aging of the population in the world. Surgical Aortic Valve Replacement (SAVR) and Transcatheter Aortic Valve Replacement (TAVR) are the cornerstone of the management of severe aortic stenosis accompanied by one or more symptoms. Moreover, an appropriate interventional treatment of CAS, in elderly patients, is a very complex decision for heart teams, to avoid bad outcomes such as operative mortality, cardiovascular and all-cause death, hospitalization for heart failure, worsening of quality of life. In fact, CAS in the elderly is not only a focal valve disease, but a very complex clinical picture with different risk factors and etiologies, differing underlying pathophysiology, large phenotypic heterogeneity in a context of subjective biological, phenotypic and functional aging until frailty and disability. In this review, we analyzed separately and in a more integrated manner, the natural and prognostic histories of the progression of aortic stenosis, the phenotypes of myocardial damage and heart failure, within the metrics and aging trajectory. The aim is to suggest, during the clinical timing of valve disease, the best interval time for an appropriate and effective interventional treatment in each older patient, beyond subjective symptoms by integration of clinical, geriatric, chemical, and advanced imaging biomarkers. Full article

Mitral annular calcification (MAC) is usually considered an incidental, benign, age-related finding without serious complications in patients evaluated for cardiovascular or pulmonary disease with imaging studies that may result in mitral regurgitation or stenosis when severe. Therefore, it is usually not considered a significant alteration. However, there is accumulating evidence that it is associated with a higher risk of cardiovascular events, such as atherosclerotic coronary artery disease, aortic artery disease, carotid artery disease, peripheral artery disease, stroke, atrial fibrillation, atrioventricular and/or intraventricular conduction disturbance, systemic embolization, infective endocarditis, heart failure and mortality. The presence of MAC also significantly influences the outcome of mitral valve transcatheter and surgical interventions. Several conditions may predispose to MAC. MAC is strongly related to cardiovascular risk factors, such as hypertension, diabetes, smoking and cardiovascular atherosclerosis, and inflammation may also play a role in the pathogenesis of MAC. Also, conditions that increase mitral valve stress, such as hypertension, aortic stenosis and hypertrophic cardiomyopathy, predispose to accelerated degenerative calcification of the mitral annulus area. Congenital disorders, e.g., Marfan syndrome and Hurler syndrome, are also associated with MAC, due to an intrinsic abnormality of the connective tissue composing the annulus. Full article

Introduction: Aortic valve disease (AVD) is an inflammatory, lipid infiltration and calcification disease that has been associated with changes in the conventional linear heart rate variability (HRV) indices showing a marked shift towards sympathetic predominance and a deterioration of the autonomic control. Objective: To explore the HRV dynamics in AVD patients through nonlinear methods by recurrence quantification analysis (RQA). Methods: In total, 127 subjects participated in a cross-sectional study categorized into three groups: healthy valve (HV), aortic valve sclerosis (AVSc), and aortic valve stenosis (AVS), as determined by echocardiographic assessment. HRV data were collected from five-minute ECG recordings at both a supine position and active standing. RQA indices were calculated using the Cross Recurrence Plot Toolbox. Results: In the supine position, patients with AVS exhibited larger determinism and trapping time than those with AVSc and HV. The analysis of these differences revealed that determinism and laminarity increased progressively from HV to AVS. In the same way, the magnitude of change (Δ) between positions decreased and presented the lowest values in AVS in most of the nonlinear indices. Conclusion: RQA indices of HRV in AVD patients indicate a rigidizing dynamic characterized by larger determinism and extended trapping times in fewer system states in relation to the severity of AVD. These findings establish a precedent for future perspective assessments for the implementation of these methods in medical software or devices. Full article

Background: To date, little is known about correlations between liver dysfunction and circulatory and cardiac abnormalities (e.g.,: mitral valve, MV) in patients with chronic liver disease (CLD). This study aimed to assess a potential parallelism between liver dysfunction and cardiovascular involvement and identify the factors associated with structural and functional MV disorders. Methods. Among 995 patients with CLD, 346 were enrolled and compared with 168 controls without liver disease. According to the degree of liver disease, patients were classified as patients with chronic hepatitis (142) or with liver cirrhosis (Child-A: 70; Child-B: 65; Child-C: 69). Results: Among the chronic hepatitis group, resting heart rate (HR) and left ventricular (LV) mass were higher than in the control group (p = 0.0008), whereas systemic vascular resistance (SVR) was lower (p = 0.01). Among cirrhotic patients, resting HR, left atrium dimensions/volumes, LV walls thickness, LV mass, cardiac output (CO), isovolumetric relaxation time (IVRT), deceleration time (DT) and prevalence of aortic stenosis were higher than in non-cirrhotic patients (p = 0.02), whereas the e/a ratio and SVR were lower (p = 0.0001). Among Child-B/C, CO, IVRT, DT, prevalence of MV regurgitation and MV calcification score were higher than in the remaining patients (p = 0.02), whereas SVR was lower (p < 0.0001). Among cirrhotic patients with MV regurgitation, Child–Pugh score, liver disease duration, resting HR, left chambers dimensions/mass, CO, IVRT, DT and MV calcification score were higher compared to patients without regurgitation (p < 0.000), whereas mean blood pressure, e/a ratio and SVR were lower (p = 0.008). At multivariate analysis, Child–Pugh score, liver disease duration, left chambers volume/mass and MV calcification score were independently associated with MV regurgitation in cirrhotic patients. Child–Pugh score and MV calcification score strongly correlated in cirrhotic patients (r = 0.68, 95% CI 0.60–0.75, p < 0.0001). Conclusions: The magnitude of cardiac morpho/functional abnormalities is associated with the severity of liver dysfunction. Structural and functional MV abnormalities could represent a novel sign of cardiac involvement in liver cirrhosis. The severity and duration of liver disease, the enlargement of cardiac chambers and leaflet calcium accumulation could play a key role. Full article

Background: Severe aortic stenosis (AS) stratified by sex has been increasingly studied in the European population. Sex-specific outcomes in Asian patients with AS remain poorly defined. Hence, we aimed to study the clinical characteristics and impact of sex in moderate-to-severe AS, undergoing both invasive and conservative interventions in an Asian cohort over 10 years. Methods: Consecutive data with echocardiographic diagnoses of AS were stratified according to gender in a tertiary academic center between 2011 and 2021. Demographics, comorbidities, and clinical outcomes were compared. Results: Seven hundred and three (703) patients were included (56%, n = 397 were female). Calcific AS was the dominant etiology in both genders. Females had higher incidences of anemia (p < 0.001) and chronic kidney disease (p = 0.026); although, females had lower incidences of cardiovascular complications of coronary artery disease (CAD) (p = 0.002) and prior acute myocardial infarction (AMI) (p = 0.015). Echocardiographically, females had a smaller left ventricular outflow tract diameter (LVOTd) (p < 0.001), LV mass (p < 0.001), and left ventricle end diastolic volume (LVEDV) (p < 0.001). Conversely, the left atrial (LA) area (p < 0.001) and volume index (LAVI) (p < 0.001) were larger in females. Females had higher average E/e’ (p = 0.010) ratios compared to males. The mean follow-up duration between genders was 4.1 ± 3.3 years. Upon univariate analysis, a greater proportion of female AS patients encountered cardiovascular (CV) hospitalization during follow-up (female: 27.5%, n = 109 vs. male: 18.3%, n = 56; p = 0.005) compared to male patients, but there were no significant differences for the outcomes of heart failure (p = 0.612), stroke (p = 0.664), and all-cause mortality (p = 0.827). Fewer females underwent aortic valve (AV) intervention compared to males (21.2% vs. 27.8%, p = 0.042), albeit with a longer duration to AV intervention (3.6 years ± 2.4 vs. 2.6 years ± 2.3, p = 0.016). In the severe AS cohort, female sex remained an independent predictor for subsequent heart failure (aHR 2.89, 95% CI 1.01–8.29, p = 0.048) and CV hospitalization (aHR 20.0, 95% CI 1.19–335, p = 0.037) after adjustments for age, ethnicity, body mass index (BMI), comorbidities, left ventricular ejection fraction (LVEF), and AV intervention. Conclusions: There was no difference in heart failure, stroke, and all-cause mortality outcomes between male and female Asian patients with moderate-to-severe AS. However, there were more cardiovascular hospitalizations, with fewer and longer duration to AV intervention in females compared to males in our cohort. Full article

Heart disease is a leading cause of mortality, with calcific aortic valve disease (CAVD) being the most prevalent subset. Being able to predict this disease in its early stages is important for monitoring patients before they need aortic valve replacement surgery. Thus, this study explored hydrodynamic, mechanical, and hemodynamic differences in healthy and very mildly calcified porcine small intestinal submucosa (PSIS) bioscaffold valves to determine any notable parameters between groups that could, possibly, be used for disease tracking purposes. Three valve groups were tested: raw PSIS as a control and two calcified groups that were seeded with human valvular interstitial and endothelial cells (VICs/VECs) and cultivated in calcifying media. These two calcified groups were cultured in either static or bioreactor-induced oscillatory flow conditions. Hydrodynamic assessments showed metrics were below thresholds associated for even mild calcification. Young’s modulus, however, was significantly higher in calcified valves when compared to raw PSIS, indicating the morphological changes to the tissue structure. Fluid–structure interaction (FSI) simulations agreed well with hydrodynamic results and, most notably, showed a significant increase in time-averaged wall shear stress (TAWSS) between raw and calcified groups. We conclude that tracking hemodynamics may be a viable biomarker for early-stage CAVD tracking. Full article

Background: Degenerative aortic valve stenosis (AS) is the most common valvular heart disease among the elderly. Once cardiac symptoms occur, current guidelines recommend aortic valve replacement. Progressive degeneration/calcification reduces leaflet mobility with gradual cardiac output (CO) impairment. Low CO might induce abnormal brain-aging with cognitive impairment and increased risk of dementia, such as Alzheimer’s disease or vascular dementia. On the contrary, cognitive improvement has been reported in patients in whom CO was restored. Transcatheter aortic valve implantation (TAVI) has proven to be a safe alternative to conventional surgery, with a similar mid-term survival and stroke risk even in low-risk patients. TAVI is associated with an immediate CO improvement, also effecting the cerebrovascular system, leading to an increased cerebral blood flow. The correlation between TAVI and cognitive improvement is still debated. The present study aims at evaluating this relationship in a cohort of AS patients where cognitive assessment before and after TAVI was available. Methods: a total of 47 patients were retrospectively selected. A transcranial Doppler ultrasound (TCD) before and after TAVI, a quality of life (QoL) score, as well as a mini-mental state examination (MMSE) at baseline and up to 36 months, were available. Results: TAVI was associated with immediate increase in mean cerebral flow at TCD. MMSE slowly increase at 36-months follow-up with improved QoL mainly for symptoms, emotions and social interactions. Conclusions: this proof-of-concept study indicates that TAVI might induce cognitive improvement in the long-term as a result of multiple factors, such as cerebral flow restoration and a better QoL. Full article

(1) Background: Transfemoral transcatheter aortic valve implantation (TAVI) has become the standard treatment for most patients with severe symptomatic aortic stenosis. Intravascular lithotripsy may facilitate transfemoral TAVI (IVL-TAVI) even in patients with severely calcified iliofemoral disease. We assessed technical aspects and clinical outcomes of this novel approach compared to alternative transaxillary access (TAX-TAVI). (2) Methods: IVL-TAVI was performed for severe iliofemoral calcifications precluding standard transfemoral access in 30 patients from 2019 to 2022 at a single academic heart center. IVL was performed as part of the TAVI procedure in all cases. Results were compared to a control group of 44 TAX-TAVI procedures performed for the same indication from 2016 to 2021. The safety outcome was a composite of all-cause death, stroke, access-related bleeding ≥ type 2 within 24 h and major vascular access site complications at 30 days. The efficacy outcome was defined as a technical success according to VARC-3. (3) Results: Median age was 78.2 [74.3, 82.6] years, 45.9% were female and mean STS-PROM was 3.6% [2.3, 6.0]. Iliofemoral calcifications were more severe in the IVL-TAVI vs. TAX-TAVI groups (lesion length: 63.0 mm [48.6, 80.3] vs. 48.5 mm [33.1, 68.8]; p = 0.043, severe calcification at target lesion: 90.0% vs. 68.2%; p = 0.047, and median arc calcification 360.0° [297.5, 360.0] vs. 360.0° [180.0, 360.0]; p = 0.033). Technical success was achieved in 93.3% vs. 81.8% (p = 0.187) in IVL- and TAX-TAVI and the safety outcome occurred in 10.0% vs. 31.8% in IVL- and TAX-TAVI (p = 0.047), respectively. (4) Conclusions: IVL-assisted transfemoral TAVI was feasible and safe with favorable outcomes compared to TAX-TAVI. IVL may further expand the number of patients eligible for transfemoral TAVI and may help overcome limitations of an alternative access. Full article

Calcific aortic valve disease (CAVD) is characterized by the fibrosis and mineralization of the aortic valve, which leads to aortic stenosis and heart failure. At the cellular level, this is due to the osteoblastic-like differentiation of valve interstitial cells (VICs), resulting in the calcification of the tissue. Unfortunately, human VICs are not readily available to study CAVD pathogenesis and the implicated mechanisms in vitro; however, adipose-derived stromal/stem cells (ASCs), carrying the patient’s specific genomic features, have emerged as a promising cell source to model cardiovascular diseases due to their multipotent nature, availability, and patient-specific characteristics. In this study, we describe a comprehensive transcriptomic analysis of tissue-engineered, scaffold-free, ASC-embedded mineralized tissue sheets using bulk RNA sequencing. Bioinformatic and gene set enrichment analyses revealed the up-regulation of genes associated with the organization of the extracellular matrix (ECM), suggesting that the ECM could play a vital role in the enhanced mineralization observed in these tissue-engineered ASC-embedded sheets. Upon comparison with publicly available gene expression datasets from CAVD patients, striking similarities emerged regarding cardiovascular diseases and ECM functions, suggesting a potential link between ECM gene expression and CAVDs pathogenesis. A matrisome-related sub-analysis revealed the ECM microenvironment promotes the transcriptional activation of the master gene runt-related transcription factor 2 (RUNX2), which is essential in CAVD development. Tissue-engineered ASC-embedded sheets with enhanced mineralization could be a valuable tool for research and a promising avenue for the identification of more effective aortic valve replacement therapies. 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