Novel Biomarkers and Their Role in the Diagnosis and Prognosis of Acute Coronary Syndrome.

The burden of cardiovascular diseases and the critical role of acute coronary syndrome (ACS) in their progression underscore the need for effective diagnostic and prognostic tools. Biomarkers have emerged as crucial instruments for ACS diagnosis, risk stratification, and prognosis assessment. Among these, high-sensitivity troponin (hs-cTn) has revolutionized ACS diagnosis due to its superior sensitivity and negative predictive value. However, challenges regarding specificity, standardization, and interpretation persist. Beyond troponins, various biomarkers reflecting myocardial injury, neurohormonal activation, inflammation, thrombosis, and other pathways are being explored to refine ACS management. This review article comprehensively explores the landscape of clinically used biomarkers intricately involved in the pathophysiology, diagnosis, and prognosis of ACS (i.e., troponins, creatine kinase MB (CK-MB), B-type natriuretic peptides (BNP), copeptin, C-reactive protein (CRP), interleukin-6 (IL-6), d-dimers, fibrinogen), especially focusing on the prognostic role of natriuretic peptides and of inflammatory indices. Research data on novel biomarkers (i.e., endocan, galectin, soluble suppression of tumorigenicity (sST2), microRNAs (miRNAs), soluble oxidized low-density lipoprotein receptor-1 (sLOX-1), F2 isoprostanes, and growth differentiation factor 15 (GDF-15)) are further analyzed, aiming to shed light on the multiplicity of pathophysiologic mechanisms implicated in the evolution of ACS. By elucidating the complex interplay of these biomarkers in ACS pathophysiology, diagnosis, and outcomes, this review aims to enhance our understanding of the evolving trajectory and advancements in ACS management. However, further research is necessary to establish the clinical utility and integration of these biomarkers into routine practice to improve patient outcomes.

Diffuse LAD and LV Thrombus as Possible Manifestation of Protein-S Deficiency in a Young Patient.

Patients with inherited hypercoagulopathies such as protein-S deficiency commonly present with venous thrombosis. However, there are rare cases of arterial thrombosis. We describe a rare case of a diffuse left anterior descending and left ventricular thrombus in a young patient with protein-S deficiency complicated with mid cerebral artery occlusion. (Level of Difficulty: Intermediate.).

Midterm Outcomes in Patients With Aortic Stenosis Treated With Contemporary Balloon-Expandable and Self-Expanding Valves: Does Valve Size Have an Impact on Outcome?

Background No data currently exist comparing the contemporary iterations of balloon-expandable (BE) Edwards SAPIEN 3/Ultra and the self-expanding (SE) Medtronic Evolut PRO/R34 valves. The aim of the study was the comparison of these transcatheter heart valves with emphasis on patients with small aortic annulus. Methods and Results In this retrospective registry, periprocedural outcomes and midterm all-cause mortality were analyzed. A total of 1673 patients (917 SE versus 756 BE) were followed up for a median of 15 months. A total of 194 patients died (11.6%) during follow-up. SE and BE groups showed similar survival at 1 (92.6% versus 90.6%) and 3 (80.3% versus 85.2%) years (Plog-rank=0.136). Compared with the BE group, patients treated with the SE device had lower peak (16.3±8 mm Hg SE versus 21.9±8 mm Hg BE) and mean (8.8±5 mm Hg SE versus 11.5±5 mm Hg BE) gradients at discharge. Conversely, the BE group demonstrated lower rates of at least moderate paravalvular regurgitation postoperatively (5.6% versus 0.7% for SE and BE valves, respectively; P<0.001). In patients treated with small transcatheter heart valves (≤26 mm for SE and ≤23 mm for BE; N=284 for SE and N=260 for BE), survival was higher among patients treated with SE valves at both 1 (96.7% SE versus 92.1% BE) and 3 (91.8% SE versus 82.2% BE) years (Plog-rank=0.042). In propensity-matched patients treated with small transcatheter heart valve, there remained a trend for higher survival among the SE group at both 1 (97% SE versus 92.3% BE) and 3 years (91.8% SE versus 78.7% BE), Plog-rank=0.096). Conclusions Real-world comparison of the latest-generation SE and BE devices demonstrated similar survival up to 3 years' follow-up. In patients with small transcatheter heart valves, there may be a trend for improved survival among those treated with SE valves.

Lipoprotein(a) and calcific aortic valve disease initiation and progression: a systematic review and meta-analysis.

Although evidence indicates the association of lipoprotein(a) [Lp(a)] with atherosclerosis, the link with calcific aortic valve disease (CAVD) is unclear. This systematic review and meta-analysis explores the connection between Lp(a) and aortic valve calcification and stenosis (AVS). We included all relevant studies, indexed in eight databases, up to February 2023. A total of 44 studies (163 139 subjects) were included, with 16 of them being further meta-analysed. Despite considerable heterogeneity, most studies support the relationship between Lp(a) and CAVD, especially in younger populations, with evidence of early aortic valve micro-calcification in elevated-Lp(a) populations. The quantitative synthesis showed higher Lp(a) levels, by 22.63 nmol/L (95% CI: 9.98-35.27), for patients with AVS, while meta-regressing the data revealed smaller Lp(a) differences for older populations with a higher proportion of females. The meta-analysis of eight studies providing genetic data, revealed that the minor alleles of both rs10455872 and rs3798220 LPA gene loci were associated with higher risk for AVS (pooled odds ratio 1.42; 95% CI: 1.34-1.50 and 1.27; 95% CI: 1.09-1.48, respectively). Importantly, high-Lp(a) individuals displayed not only faster AVS progression, by a mean difference of 0.09 m/s/year (95% CI: 0.09-0.09), but also a higher risk of serious adverse outcomes, including death (pooled hazard ratio 1.39; 95% CI: 1.01-1.90). These summary findings highlight the effect of Lp(a) on CAVD initiation, progression and outcomes, and support the early onset of Lp(a)-related subclinical lesions before clinical evidence.

The Role of Rehabilitation in Arterial Function Properties of Convalescent COVID-19 Patients.

Coronavirus disease (COVID-19) is a respiratory disease, although arterial function involvement has been documented. We assess the impact of a post-acute COVID-19 rehabilitation program on endothelium-dependent vasodilation and arterial wall properties. We enrolled 60 convalescent patients from COVID-19 and one-month post-acute disease, who were randomized at a 1:1 ratio in a 3-month cardiopulmonary rehabilitation program (study group) or not (control group). Endothelium-dependent vasodilation was evaluated by flow-mediated dilation (FMD), and arterial wall properties were evaluated by carotid-femoral pulse wave velocity (cf-PWV) and augmentation index (AIx) at 1 month and at 4 months post-acute disease. FMD was significantly improved in both the study (6.2 ± 1.8% vs. 8.6 ± 2.4%, p < 0.001) and control groups (5.9 ± 2.2% vs. 6.6 ± 1.8%, p = 0.009), but the improvement was significantly higher in the study group (rehabilitation) (p < 0.001). PWV was improved in the study group (8.2 ± 1.3 m/s vs. 6.6 ± 1.0 m/s, p < 0.001) but not in the control group (8.9 ± 1.8 m/s vs. 8.8 ± 1.9 m/s, p = 0.74). Similarly, AIx was improved in the study group (25.9 ± 9.8% vs. 21.1 ± 9.3%, p < 0.001) but not in the control group (27.6 ± 9.2% vs. 26.2 ± 9.8 m/s, p = 0.15). Convalescent COVID-19 subjects of the study group (rehabilitation) with increased serum levels of circulating IL-6 had a greater reduction in FMD. Conclusively, a 3-month cardiopulmonary post-acute COVID-19 rehabilitation program improves recovery of endothelium-dependent vasodilation and arteriosclerosis.

Residual Right-to-Left-Shunt Following Transcatheter Patent Foramen Ovale Closure: The Role of Antithrombotic Treatment.

BACKGROUND: Transcatheter closure of patent foramen ovale (PFO) is a highly effective therapy for patients with left circulation thromboembolism, not attributable to other conditions. OBJECTIVES: This retrospective cohort study investigates the impact of baseline foramen ovale anatomy on the severity of the postclosure shunt. METHODS: Patients with PFO, who underwent percutaneous closure, were followed up for at least 5 years postimplantation. Patients were classified into two groups based on the presence of high-risk features of the baseline PFO anatomy. At the follow-up follow-up, residual right-to-left shunt was assessed for the high and non-highrisk anatomy groups, via transcranial Doppler at rest and after performing the Valsalva maneuver, with the injection of agitated saline. RESULTS: 38 patients were examined after a mean follow-up period of 9 ± 3 years after implantation. After retrospective evaluation of the baseline transthoracic and transesophageal echo studies, 14 patients with high-risk PFO anatomy were identified. The degree of the residual right-to-left shunt, as assessed by the number of microbubbles was higher in the high-risk PFO anatomy group compared to the non-high-risk group, both at rest [1.50 (IQR: 0.00-3.25) vs. 0.00 (IQR: 0.00-0.00), p < 0.001] and post-Valsalva maneuver [7.50 (IQR: 1.50- 10.25) vs. 0.00 (IQR: 0.00-3.75), p = 0.003]. Furthermore, in the high-risk group, more microbubbles were detected at rest (p = 0.008) and post-Valsalva (p = 0.002) in subjects without antiplatelet treatment compared to subjects on prolonged antiplatelet therapy. CONCLUSION: Baseline PFO anatomy affects the severity of the residual right-to-left shunt. Prolonged antiplatelet therapy may benefit patients with high-risk anatomical features.

The Role of Cell-derived Microparticles in Cardiovascular Diseases: Current Concepts.

Cardiovascular disease remains the main cause of human morbidity and mortality in developed countries. Microparticles (MPs) are small vesicles originating from the cell membrane as a result of various stimuli and particularly of biological processes that constitute the pathophysiology of atherosclerosis, such as endothelial damage. They form vesicles that can transfer various molecules and signals to remote target cells without direct cell-to-cell interaction. Circulating microparticles have been associated with cardiovascular diseases. Therefore, many studies have been designed to further investigate the role of microparticles as biomarkers for diagnosis, prognosis, and disease monitoring. To this concept, the pro-thrombotic and atherogenic potential of platelets and endothelial-derived MPs have gained research interest, especially concerning accelerated atherosclerosis and triggering as well as prognosis of an acute coronary syndrome. MPs, especially those of endothelial origin, have been investigated in different clinical scenarios of heart failure and in association with left ventricular loading conditions. Finally, most cardiovascular risk factors present unique features in the circulating MPs population, highlighting their pathophysiologic link to cardiovascular disease progression. In this review article, we present a synopsis of the biogenesis and characteristics of microparticles, as well as the most recent data concerning their implication in cardiovascular settings.

A case report of left ventricular thrombus formation following aggressive decongestion treatment.

Background: Intracardiac thrombi are a complication associated with cardiomyopathies. In heart failure with reduced ejection fraction, there is a hypercoagulable state that can increase the incidence of left ventricular thrombus and result in higher risk of thromboembolism, either manifested as stroke or as peripheral thromboembolic event. Haemoconcentration following decongestion treatment may enhance blood viscosity. Case summary: A 63-year-old man with known long-standing heart failure (HF) of ischaemic aetiology and not any prothrombotic risk, admitted with congestive HF and treated with aggressive decongestion treatment with intravenous loop diuretics. During his hospital stay, and following decongestion and haemoconcentration, a left ventricular (LV) intracardiac thrombus formation was detected by echocardiography, which occurred in the absence of a recent myocardial infarction or adverse LV remodelling. The patient was treated with oral anticoagulation therapy. There was a complete resolution of the thrombus on repeat transthoracic echocardiography after 4 weeks of treatment. Discussion: Aggressive decongestive treatment, haemoconcentration and increased blood viscosity following HF decompensation may serve as a trigger for intracardiac thrombus formation under the appropriate prothrombotic background. Appropriate primary antithrombotic prophylaxis is an issue raised concerns and vulnerable patients need closed clinical and imaging follow-up.

The Role of Endothelial Related Circulating Biomarkers in COVID-19. A Systematic Review and Meta-analysis.

BACKGROUND: Several studies have revealed the link between Coronavirus Disease 2019 (COVID-19) and endothelial dysfunction. To better understand the global pattern of this relationship, we conducted a meta-analysis on endothelial biomarkers related to COVID-19 severity. METHODS: We systematically searched the literature up to March 10, 2021, for studies investigating the association between COVID-19 severity and the following endothelial biomarkers: Intercellular Adhesion Molecule 1 (ICAM-1), Vascular Cell Adhesion Molecule 1 (VCAM-1), E-selectin, P-selectin, Von Willebrand Factor Antigen (VWFAg), soluble Thrombomodulin (sTM), Mid-regional pro-adrenomedullin (MR-proADM), and Angiopoietin-2 (Ang-2). Pooled estimates and mean differences (PMD) for each biomarker were reported. RESULTS: A total of 27 studies (n=2213 patients) were included. Critically ill patients presented with higher levels of MR-proADM (PMD: 0.71 nmol/L, 95% CI: 0.22 to 1.20 nmol/L, p=0.02), E-selectin (PMD: 13,32 pg/ml, 95% CI: 4,89 to 21,75 pg/ml, p=0.008), VCAM-1 (PMD: 479 ng/ml, 95% CI: 64 to 896 ng/ml, p=0.03), VWF-Ag (PMD: 110.5 IU/dl, 95% CI: 44.8 to 176.1 IU/dl, p=0.04) and Ang-2 (PMD: 2388 pg/ml, 95% CI: 1121 to 3655 pg/ml, p=0.003), as compared to non-critically ill ones. ICAM-1, P-selectin and thrombomodulin did not differ between the two groups (p>0.05). CONCLUSION: Endothelial biomarkers display significant heterogeneity in COVID-19 patients, with higher MR-proADM, E-selectin, VCAM-1, VWF-Ag, and Ang-2 levels being associated with increased severity. These findings strengthen the evidence on the key role of endothelial dysfunction in disease progress.

Comparison of Ticagrelor Versus Clopidogrel on Cerebrovascular Microembolic Events and Platelet Inhibition during Transcatheter Aortic Valve Implantation.

The impact of the antiplatelet regimen and the extent of associated platelet inhibition on cerebrovascular microembolic events during transcatheter aortic valve implantation (TAVI) are unknown. Our aim was to evaluate the effects of ticagrelor versus clopidogrel and of platelet inhibition on the number of cerebrovascular microembolic events in patients undergoing TAVI. Patients scheduled for TAVI were randomized previous to the procedure to either aspirin and ticagrelor or to aspirin and clopidogrel. Platelet inhibition was expressed in P2Y12 reaction units (PRU) and percentage of inhibition. High intensity transient signals (HITS) were assessed with transcranial Doppler (TCD). Safety outcomes were recorded according to the VARC-2 definitions. Among 90 patients randomized, 6 had an inadequate TCD signal. The total number of procedural HITS was lower in the ticagrelor group (416.5 [324.8, 484.2]) (42 patients) than in the clopidogrel group (723.5 [471.5, 875.0]) (42 patients), p <0.001. After adjusting for the duration of the procedure, diabetes, extra-cardiac arteriopathy, BMI, hypertension, aortic valve calcium content, procedural ACT, and pre-implantation balloon valvuloplasty, patients on ticagrelor had on average 256.8 (95% CI: [-335.7, -176.5]) fewer total procedural HITS than patients on clopidogrel. Platelet inhibition was greater with ticagrelor 26 [10, 74.5] PRU than with clopidogrel 207.5 (120 to 236.2) PRU, p <0.001, and correlated significantly with procedural HITS (r = 0.5, p <0.05). In conclusion, ticagrelor resulted in fewer procedural HITS, compared with clopidogrel, in patients undergoing TAVI, while achieving greater platelet inhibition.

Transcatheter closure of paravalvular leak: Multicenter experience and follow-up.

BACKGROUND: Paravalvular leak (PVL) is a common complication following valve replacement, which leads to heart failure and hemolysis. Transcatheter PVL closure has emerged as a reliable alternative with promising results. We quote the combined three-center experience of PVL patients treated percutaneously. METHODS: Consecutive patients treated percutaneously for PVL were retrospectively studied. Procedural characteristics, inhospital, and long-term clinical outcomes were assessed. Technical (successful deployment) and clinical (NYHA and/or hemolysis improvement) success were evaluated. RESULTS: In total, 39 patients treated for PVL in either the aortic (12 patients) or the mitral (27 patients) position were studied. Amplatzer Vascular Plug III was the most commonly used device among the 45 devices totally implanted. Postprocedurally, the rates of at least moderate PVL (87.5% preprocedurally vs 10.5% at discharge) and functional status (mean NYHA class 2.8 ± 0.7 on admission vs 1.5 ± 0.8 at follow-up) were statistically significantly improved. Total population technical success rate was 89.7%, being comparable between patients treated for mitral or aortic valve PVLs (92.6% vs 83.3%, respectively). Clinical success was achieved in 82.1% of patient cohort without statistical difference among those with isolated aortic or mitral PVL or among those with PVL closure an indication of heart failure or hemolysis. During a mean follow-up of 33.5 months, five patients died, including one periprocedural death. CONCLUSIONS: This multicenter recorded experience confirms that percutaneous PVL closure can be performed with high technical and clinical success rates and limited complications that lead to significant PVL reduction and functional status improvement.

MicroRNAs in the Management of Heart Failure.

BACKGROUND: In recent years much research has been devoted to the deployment of biomarkers in the field of heart failure. OBJECTIVES: To study the potential of post-transcriptional regulation by microRNAs on the diagnosis, management and therapy of heart failure. METHODS: Literature search focuses on the role of microRNAs in heart failure. RESULTS: MicroRNAs are expressed and regulated in the course of the pathological manifestations of heart failure (HF). This wide and uncharted area of genetic imprints consisting of small non-coding RNA molecule is upregulated and released into the bloodstream from organs under certain conditions and or stress. The use of genetically based strategies for the management of HF has gained great interest in the field of biomedical science because they can be used as biomarkers providing information regarding cardiac status and function. They also appear as promising tools with therapeutic potential because of their ability to induce changes at the cellular level without creating alterations in the gene sequence. In addition, with the advances in genomic sequencing, quantification and synthesis in technologies of microRNAs identification as well as the growing knowledge of the biology of miRNAs and their involvement in HF, it is expected to favorably affect the prognosis of HF patients. CONCLUSION: MicroRNAs are involved in the regulation of multibiological processes involved in the progress of heart failure. More studies are needed to achieve a clinical valuable implementation of microRNAs in the management of HF.

Personalized Assessment of the Coronary Atherosclerotic Arteries by Intravascular Ultrasound Imaging: Hunting the Vulnerable Plaque.

The term "vulnerable plaque" is commonly used to refer to an atherosclerotic plaque that is prone to rupture and the formation of thrombosis, which can lead to several cardiovascular and cerebrovascular events. Coronary artery atherosclerosis has a wide variety of different phenotypes among patients who may have a substantially variable risk for plaque rupture and cardiovascular events. Mounting evidence has proposed three distinctive histopathological mechanisms: plaque rupture, plaque erosion and calcified nodules. Studies have demonstrated the characteristics of plaques with high vulnerability such as the presence of a thin fibrous cap, a necrotic lipid-rich core, abundant infiltrating macrophages and neovascularization. However, traditional coronary angiographic imaging fails to determine plaque vulnerability features, and its ability to individualize treatment strategies is limited. In recent decades, catheter-based intravascular ultrasound imaging (IVUS) modalities have been developed to identify vulnerable plaques and ultimately vulnerable patients. The aim is to individualize prediction, prevention and treatment of acute coronary events based on the identification of specific features of high-risk atherosclerotic plaques, and to identify the most appropriate interventional procedures for their treatment. In this context, the aim of this review is to discuss how personalized assessment of coronary atherosclerotic arteries can be achieved by intravascular ultrasound imaging focusing on vulnerable plaque detection.

Reduction of Fluoroscopic Exposure Using a New Fluoroscopy Integrating Technology in a 3D-Mapping System During Pulmonary Vein Isolation With a Circular Multipolar Irrigated Catheter.

Pulmonary vein isolation (PVI) is a cornerstone therapy in patients with atrial fibrillation (AF). With increasing numbers of PVI procedures, demand arises to reduce the cumulative fluoroscopic radiation exposure for both the physician and the patient. New technologies are emerging to address this issue. Here, we report our first experiences with a new fluoroscopy integrating technology in addition to a current 3D-mapping system. The new fluoroscopy integrating system (FIS) with 3D-mapping was used prospectively in 15 patients with AF. Control PVI cases (n = 37) were collected retrospectively as a complete series. Total procedure time (skin to skin), fluoroscopic time, and dose-area-product (DAP) data were analyzed. All PVI procedures were performed by one experienced physician using a commercially available circular multipolar irrigated ablation catheter. All PVI procedures were successfully undertaken without major complications. Baseline characteristics of the two groups showed no significant differences. In the group using the FIS, the fluoroscopic time and DAP were significantly reduced from 571 ± 187 seconds versus 1011 ± 527 seconds (P = 0.0029) and 4342 ± 2073 cGycm(2) versus 6208 ± 3314 cGycm(2) (P = 0.049), respectively. Mean procedure time was not significantly affected and was 114 ± 31 minutes versus 104 ± 24 minutes (P = 0.23) by the FIS.The use of the new FIS with the current 3D-mapping system enables a significant reduction of the total fluoroscopy time and DAP compared to the previous combination of 3D-mapping system plus normal fluoroscopy during PVI utilizing a circular multipolar irrigated ablation catheter. However, the concomitant total procedure time is not affected. Thus, the new system reduces the radiation exposure for both the physicians and patients.