Search Results (165)

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

Pathologies of the heart (e.g., ischemic disease, valve fibrosis and calcification, progressive myocardial fibrosis, heart failure, and arrhythmogenic disorders) stem from the irreversible deterioration of cardiac tissues, leading to severe clinical consequences. The limited regenerative capacity of the adult myocardium and the architectural complexity of the heart present major challenges for tissue engineering. However, recent advances in biomaterials and biofabrication techniques have opened new avenues for recreating functional cardiac tissues. Particularly relevant in this context is the integration of biomimetic design principles, such as structural anisotropy, mechanical and electrical responsiveness, and tissue-specific composition, into 3D bioprinting platforms. This review aims to provide a comprehensive overview of current approaches in cardiac bioprinting, with a focus on how structural and functional biomimicry can be achieved using advanced hydrogels, bioprinting techniques, and post-fabrication stimulation. By critically evaluating materials, methods, and applications such as patches, vasculature, valves, and chamber models, we define the state of the art and highlight opportunities for developing next-generation bioengineered cardiac constructs. Full article

Background: Aortic stenosis (AS) has long been considered a degenerative disease and is typically diagnosed in older men at an advanced stage. However, accumulating evidence has highlighted the similarities between AS and atherosclerosis, particularly regarding shared risk factors and overlapping pathophysiological mechanisms. This connection has led to a paradigm shift, suggesting that AS may be preventable in its early stages. Methods: This narrative review synthesizes the existing literature exploring the parallels between AS and atherosclerosis, focusing on common risk factors, pathogenic pathways, and evolving therapeutic strategies. Clinical trials and translational studies were examined to assess the effectiveness of atherosclerosis-based treatments for AS. Results: Multiple studies have confirmed the shared inflammatory, lipid-mediated, and calcific mechanisms of AS and atherosclerosis. Despite these similarities, therapeutic strategies effective in atherosclerosis, such as statin therapy, have not consistently shown benefits in AS. New medical approaches aim to delay aortic valve replacement and reduce the associated morbidity. The partially overlapping pathogenesis continues to guide future research. Conclusions: While AS and atherosclerosis share several pathogenic features, their clinical courses and treatment responses diverge. Understanding the limits and potential of their overlap may inform future preventive and therapeutic strategies. Earlier detection and targeted intervention in AS remain key goals, drawing on insights from cardiovascular disease management. Full article

Mitral valve disease, particularly in the context of extensive mitral annular calcification (MAC), poses significant challenges for traditional surgical management. Transcatheter mitral valve replacement (TMVR) has emerged as a promising alternative for high-risk and inoperable patients, driven by rapid advancements in valve technology, imaging techniques, and procedural strategies. Nevertheless, complications such as paravalvular leak (PVL), left ventricular outflow tract (LVOT) obstruction, and hemolysis remain obstacles to optimal outcomes, particularly in patients with complex annular anatomy. We present the case of an 89-year-old female with severe mitral stenosis and MAC who developed acute hemolytic anemia following experimental TMVR using the Edwards SAPIEN S3 valve. This case serves as a platform to explore recent advances in TMVR, including novel device platforms, enhanced imaging modalities for pre-procedural planning, innovative deployment strategies, and emerging adjunctive techniques aimed at reducing complications. Through this case, we underscore persistent challenges and emphasize the importance of meticulous patient selection and vigilant follow-up. Despite substantial progress, TMVR in the setting of MAC remains high-risk, demanding continued innovation in valve design, refined patient stratification, and improved peri-procedural management to enhance outcomes and mitigate risks such as hemolysis. 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

Transcatheter aortic valve replacement (TAVR) has become a well-established treatment for severe aortic stenosis across all levels of surgical risk. While transfemoral access remains the default approach, complications arising from vascular access—especially in patients with peripheral artery disease (PAD)—pose significant challenges. Hostile vascular access, characterized by narrow vessel diameters, severe calcification, and tortuosity, complicates the procedure and necessitates alternative strategies. Recent advancements, such as intravascular lithotripsy (IVL), have shown promise in managing severely calcified arteries, improving the feasibility of transfemoral TAVR in patients previously considered ineligible. IVL uses pulsatile sonic waves to fragment arterial calcifications, enhancing vessel compliance and facilitating safe device delivery. Studies have demonstrated that IVL-assisted TAVR improves procedural success and reduces complications in patients with PAD. Additionally, orbital atherectomy, an adjunctive therapy targeting both concentric and eccentric calcifications, may complement the management of complex arterial calcification. The Hostile and passage–puncture scores offer valuable risk stratification tools for predicting vascular complications, aiding in better access site selection. Post-procedural echocardiography, particularly femoral artery sonography, may also play a role in detecting vascular complications early, enabling timely intervention. Finally, alternative access sites are increasingly being explored, with emerging data helping to guide the final access site decision. As TAVR continues to expand into lower risk populations, optimizing vascular access strategies remains essential to improving procedural outcomes. This review highlights the importance of preoperative imaging, endovascular techniques, and post-procedural monitoring in overcoming vascular challenges and ensuring successful TAVR outcomes. Full article

Background: Patients with heterozygous familial hypercholesterolemia (HeFH) are at a high risk of atherosclerotic cardiovascular disease. The coronary artery calcification (CAC) score by the Ct-scan Agatston calcium score (ACS) > 100 classifies FH at a higher risk. The echocardiographic calcium score (ECS) evaluates aortic valve calcifications and is considered a good predictor of the atherosclerotic burden and cardiovascular outcome. Objective: To test the ECS as a predictor of ACS > 100 in a HeFH cohort. Methods: A coronary calcium CT scan with the calculation of ACS and an at rest-transthoracic echocardiogram with ECS evaluation were performed in 81 HeFH patients. Patients were divided into two groups according to the ACS: high-risk ACS patients (High-ACS) with Agatston value > 100 and low risk ACS patients (Low-ACS) with Agatston value ≤ 100. Patients were stratified according to ECS = 0 or ECS > 0. Results: High-ACS patients were older than Low-ACS patients; BMI, waist circumference, and blood systolic pressure were significantly higher (p < 0.001) in High-ACS patients. The ECS predicted an ACS > 100 with sensitivity = 0.84, specificity = 0.89, accuracy = 0.86, and precision = 0.76. Conclusions: The ECS could be a good surrogate of a coronary calcium CT scan for ACS evaluation in the specific subset of HeFH patients. 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

Background: Calcific aortic valve disease (CAVD) is a highly prevalent disease, especially in the elderly population, but there are no effective drug therapies other than aortic valve repair or replacement. CAVD develops preferentially on the fibrosa side, while the ventricularis side remains relatively spared through unknown mechanisms. We hypothesized that the fibrosa is prone to the disease due to side-dependent differences in transcriptomic patterns and cell phenotypes. Methods: To test this hypothesis, we performed single-cell RNA sequencing using a new method to collect endothelial-enriched samples independently from the fibrosa and ventricularis sides of freshly obtained human aortic valve leaflets from five donors, ranging from non-diseased to fibrocalcific stages. Results: From the 82,356 aortic valve cells analyzed, we found 27 cell clusters, including seven valvular endothelial cell (VEC), nine valvular interstitial cell (VIC), and seven immune, three transitional, and one stromal cell population. We identified several side-dependent VEC subtypes with unique gene expression patterns. Homeostatic VIC clusters were abundant in non-diseased tissues, while VICs enriched with fibrocalcific genes and pathways were more prevalent in diseased leaflets. Furthermore, homeostatic macrophage (MΦ) clusters decreased while inflammatory MΦ and T-cell clusters increased with disease progression. A foamy MΦ cluster was increased in the fibrosa of mildly diseased tissues. Some side-dependent VEC clusters represented non-diseased, protective phenotypes, while others were CAVD-associated and were characterized by genes enriched in pathways of inflammation, endothelial–mesenchymal transition, apoptosis, proliferation, and fibrosis. Interestingly, we found several activator protein-1 (AP-1)-related transcription factors (FOSB, FOS, JUN, JUNB) and EGR1 to be upregulated in the fibrosa and diseased aortic valve leaflets. Conclusions: Our results showed that VECs are highly heterogeneous in a side- and CAVD-dependent manner. Unique VEC clusters and their differentially regulated genes and pathways found in the fibrosa of diseased tissues may represent novel pathogenic mechanisms and potential therapeutic targets. Full article

A significant role in the pathogenesis of CAVD is played by innate immunity cells, such as macrophages. In stenotic valves, macrophages have enhanced inflammatory activity, and the population’s balance is shifted toward pro-inflammatory ones. Pro-inflammatory macrophages release cytokines, chemokines, and microRNA, which can directly affect the resident valvular cells and cause valve calcification. In CAVD patients, macrophages may have more pronounced pro-inflammatory properties, enhanced not only by paracrine signals but also by juxtacrine Notch signaling and epigenetic factors, which influence the maturation of macrophages’ progenitors. In this review, we observe the accumulated data on the involvement of macrophages in CAVD development via paracrine and juxtacrine interactions. Full article

This paper reviews recent biomechanical studies on heart valve flutter. The function of the heart valves is essential for maintaining effective blood circulation. Heart valve flutter is a kind of small vibration phenomenon like a flag fluttering in the wind, which is related to many factors such as a thrombus, valve calcification, regurgitation, and hemolysis and material fatigue. This vibration phenomenon is particularly prevalent in valve replacement patients. The biomechanical implications of flutter are profound and can lead to micro-trauma of valve tissue, accelerating its degeneration process and increasing the risk of thrombosis. We conducted a systematic review along with a critical appraisal of published studies on heart valve flutter. In this review, we summarize and analyze the existing literature; discuss the detection methods of frequency and amplitude of heart valve flutter, and its potential effects on valve function, such as thrombosis and valve degeneration; and discuss some possible ways to avoid flutter. These findings are important for optimizing valve design, diagnosing diseases, and developing treatment strategies. Full article

Lipoprotein (a) is a complex lipid molecule that has sparked immense interest in recent years, after studies demonstrated its significant association with several cardiovascular conditions. Lp(a) promotes cardiovascular disease through its combined proatherogenic, pro-inflammatory, and prothrombotic effects. While the measurement of Lp(a) has become widely available, effective methods to reduce its concentration are currently limited. However, emerging data from ongoing clinical trials involving antisense oligonucleotides have indicated promising outcomes in effectively reducing Lp(a) concentrations. This may serve as a potential therapeutic target in the management and prevention of myocardial infarction, calcific aortic stenosis, and cerebrovascular accidents. In contrast, the role of Lp(a) in atrial fibrillation, in-stent restenosis, cardiac allograft vasculopathy, and bioprosthetic aortic valve degeneration remains unclear. This review article aims to thoroughly review the existing literature and provide an updated overview of the evidence surrounding the association of Lp(a) and these cardiovascular diseases. We seek to highlight controversies in the existing literature and offer directions for future investigations to better understand Lp(a)’s precise role in these conditions, while providing a summary of its unique molecular characteristics. 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