Metabolic Dysfunction Associated Liver Disease in Patients Undergoing Coronary Computed Tomography Angiography.

In this single-center cross-sectional study on patients undergoing coronary computed tomography angiography (CCTA), we assessed the prognostic significance of metabolic dysfunction associated steatotic liver disease (MASLD), metabolic syndrome (MetS), and CCTA-derived parameters for predicting major adverse cardiovascular events (MACE). Over a mean follow-up of 26.9 months, 2038 patients were analyzed, with 361 (17.7%) experiencing MACE. MASLD was associated with a higher MACE incidence (25.90% vs. 14.71% without MASLD, p < 0.001). Cox regression revealed significant associations between MASLD, coronary calcium score (CCS), number of plaques (NoP), epicardial fat volume (EFV), and MACE, with hazard ratios of 1.843, 1.001, 1.097, and 1.035, respectively (p < 0.001 for all). A composite risk score integrating CCS, NoP, EFV, and MASLD demonstrated superior predictive value for MACE (AUC = 0.948) compared to individual variables (p < 0.0001 for all). In conclusion, MASLD is linked to an elevated risk of MACE, and a comprehensive risk-scoring system incorporating imaging and clinical factors enhances MACE prediction accuracy.

Cardiac Resynchronization Therapy and Left Atrial Remodeling: A Novel Insight?

Cardiac resynchronization therapy (CRT) restores ventricular dyssynchrony, improving left ventricle (LV) systolic function, symptoms, and outcome in patients with heart failure, systolic dysfunction, and prolonged QRS interval. The left atrium (LA) plays tremendous roles in maintaining cardiac function, being often inflicted in various cardiovascular diseases. LA remodeling implies structural-dilation, functional-altered phasic functions, and strain and electrical-atrial fibrillation remodeling. Until now, several important studies have approached the relationship between LA and CRT. LA volumes can predict responsiveness to CRT, being also associated with improved outcome in these patients. LA function and strain parameters have been shown to improve after CRT, especially in those who were positive responders to it. Further studies still need to be conducted to comprehensively characterize the impact of CRT on LA phasic function and strain, and, also, in conjunction with its impact on functional mitral regurgitation and LV diastolic dysfunction. The aim of this review was to provide an overview of current available data regarding the relation between CRT and LA remodeling.

Cardiac Resynchronization Therapy and Hypertrophic Cardiomyopathy: A Comprehensive Review.

Hypertrophic cardiomyopathy (HCM) is an inherited primary myocardial disease characterized by asymmetrical/symmetrical left ventricle (LV) hypertrophy, with or without LV outflow tract (LVOT) dynamic obstruction, and poor prognosis. Cardiac resynchronization therapy (CRT) has emerged as a minimally invasive tool for patients with heart failure (HF) with decreased LV ejection fraction (LVEF) and prolonged QRS duration of over 120 ms with or without left bundle branch block (LBBB). Several HCM patients are at risk of developing LBBB because of disease progression or secondary to septal myomectomy, while others might develop HF with decreased LVEF, alleged end-stage/dilated HCM, especially those with thin myofilament mutations. Several studies have shown that patients with myectomy-induced LBBB might benefit from left bundle branch pacing or CRT to relieve symptoms, improve exercise capacity, and increase LVEF. Otherwise, patients with end-stage/dilated HCM and prolonged QRS interval could gain from CRT in terms of NYHA class improvement, LV systolic performance increase and, to some degree, LV reverse remodeling. Moreover, several electrical and imaging parameters might aid proper selection and stratification of HCM patients to benefit from CRT. Nonetheless, current available data are scarce and further studies are still required to accurately clarify the view. This review reassesses the importance of CRT in patients with HCM based on current research by contrasting and contextualizing data from various published studies.

Parkinson's disease and cardiovascular involvement: Edifying insights (Review).

Parkinson's disease (PD) is one of the most common neurodegenerative illnesses, and is a major healthcare burden with prodigious consequences on life-quality, morbidity, and survival. Cardiovascular diseases are the leading cause of mortality worldwide and growing evidence frequently reports their co-existence with PD. Cardiac dysautonomia due to autonomic nervous system malfunction is the most prevalent type of cardiovascular manifestation in these patients, comprising orthostatic and postprandial hypotension, along with supine and postural hypertension. Moreover, many studies have endorsed the risk of patients with PD to develop ischemic heart disease, heart failure and even arrhythmias, but the underlying mechanisms are not entirely clear. As importantly, the medication used in treating PD, such as levodopa, dopamine agonists or anticholinergic agents, is also responsible for cardiovascular adverse reactions, but further studies are required to elucidate the underlying mechanisms. The purpose of this review was to provide a comprehensive overview of current available data regarding the overlapping cardiovascular disease in patients with PD.

Cardiac Magnetic Resonance Imaging in Appraising Myocardial Strain and Biomechanics: A Current Overview.

Subclinical alterations in myocardial structure and function occur early during the natural disease course. In contrast, clinically overt signs and symptoms occur during late phases, being associated with worse outcomes. Identification of such subclinical changes is critical for timely diagnosis and accurate management. Hence, implementing cost-effective imaging techniques with accuracy and reproducibility may improve long-term prognosis. A growing body of evidence supports using cardiac magnetic resonance (CMR) to quantify deformation parameters. Tissue-tagging (TT-CMR) and feature-tracking CMR (FT-CMR) can measure longitudinal, circumferential, and radial strains and recent research emphasize their diagnostic and prognostic roles in ischemic heart disease and primary myocardial illnesses. Additionally, these methods can accurately determine LV wringing and functional dynamic geometry parameters, such as LV torsion, twist/untwist, LV sphericity index, and long-axis strain, and several studies have proved their utility in prognostic prediction in various cardiovascular patients. More recently, few yet important studies have suggested the superiority of fast strain-encoded imaging CMR-derived myocardial strain in terms of accuracy and significantly reduced acquisition time, however, more studies need to be carried out to establish its clinical impact. Herein, the current review aims to provide an overview of currently available data regarding the role of CMR in evaluating myocardial strain and biomechanics.

Left atrial geometric and functional remodeling parameters measured by cardiac magnetic resonance imaging and outcome prediction in patients with severe aortic stenosis.

BACKGROUND: Emerging studies are beginning to describe the role of afflicted left atrium (LA) function and strain in cardiovascular diseases including aortic stenosis (AS), especially for risk stratification and outcome prediction. Cardiac magnetic resonance imaging (CMR) is becoming increasingly useful in determining LA parameters; however, in patients with AS, this approach has not been applied yet. AIMS: This study sought to evaluate the role of CMR in characterizing LA geometry and function in patients with severe AS. METHODS: We prospectively evaluated 70 patients with symptomatic severe AS and 70 controls. LA volumes, function, and strain were determined using CMR. A composite outcome (cardiac death, ventricular tachyarrhythmias, and heart failure hospitalization) was evaluated over a median of 13 months. Time-to-event outcomes were analyzed accordingly. RESULTS: Besides increased LA volumes (LAVs) and LA sphericity index (LASI) (P <0.001), LA phasic functions and strain were considerably defective in patients with AS (all P <0.001). LV mass (LVM), end-diastolic and end-systolic volumes were also significantly associated withal LA strain parameters (P <0.001). Regarding outcome prediction, decreased total (LA-εt), active (LA-εa), and passive strain (LA-εp), along with enhanced LASI were independently associated with outcome (P <0.001). Time-to-event analysis showed a significantly higher risk to reach the composite outcome for LA-εt <31.1% (hazard ratio [HR], 6.981; 95% confidence interval [CI], 2.74-17.77; P <0.001), LA-εp <14.5% (HR, 2.68; 95% CI, 1.00-7.18; P <0.01), and LA-εa <21.2% (HR, 2.02; 95% CI, 1.07-3.83, P <0.03). CONCLUSION: Patients with severe AS have a significantly remodeled LA, with impaired phasic function and strain. Amongst all CMR parameters, LAVmin, LASI, LAPF, and LA-εp appear to be independent predictors for outcomes.

The Role of Circulating Collagen Turnover Biomarkers and Late Gadolinium Enhancement in Patients with Non-Ischemic Dilated Cardiomyopathy.

Background: Myocardial scarring is a primary pathogenetic process in nonischemic dilated cardiomyopathy (NIDCM) that is responsible for progressive cardiac remodeling and heart failure, severely impacting the survival of these patients. Although several collagen turnover biomarkers have been associated with myocardial fibrosis, their clinical utility is still limited. Late gadolinium enhancement (LGE) determined by cardiac magnetic resonance imaging (CMR) has become a feasible method to detect myocardial replacement fibrosis. We sought to evaluate the association between collagen turnover biomarkers and replacement myocardial scarring by CMR and, also, to test their ability to predict outcome in conjunction with LGE in patients with NIDCM. Method: We conducted a prospective study on 194 patients (48.7 ± 14.3 years of age; 74% male gender) with NIDCM. The inclusion criteria were similar to those for the definition of NIDCM, performed exclusively by CMR: (1) LV dilation with an LV end-diastolic volume (LVEDV) of over 97 mL/m2; (2) global LV dysfunction, expressed as a decreased LVEF of under 45%. CMR was used to determine the presence and extent of LGE. Several collagen turnover biomarkers were determined at diagnosis, comprising galectin-3 (Gal3), procollagen type I carboxy-terminal pro-peptide (PICP) and N-terminal pro-peptide of procollagen type III (PIIINP). A composite outcome (all-cause mortality, ventricular tachyarrhythmias, heart failure hospitalization) was ascertained over a median of 26 months. Results: Gal3, PICP and PIIINP were considerably increased in those with LGE+ (p < 0.001), also being directly correlated with LGE mass (r2 = 0.42; r2 = 0.44; r2 = 0.31; all p < 0.001). Receiver operating characteristic (ROC) analysis revealed a significant ability to diagnose LGE, with an area under the ROC of 0.816 for Gal3, 0.705 for PICP, and 0.757 for PIIINP (all p < 0.0001). Kaplan−Meier analysis showed that at a threshold of >13.8 ng/dL for Gal3 and >97 ng/dL for PICP, they were able to significantly predict outcome (HR = 2.66, p < 0.001; HR = 1.93, p < 0.002). Of all patients, 17% (n = 33) reached the outcome. In multivariate analysis, after adjustment for covariates, only LGE+ and Gal3+ remained independent predictors for outcome (p = 0.008; p = 0.04). Nonetheless, collagen turnover biomarkers were closely related to HF severity, providing incremental predictive value for severely decreased LVEF of under 30% in patients with NIDCM, beyond that with LGE alone. Conclusions: In patients with NIDCM, circulating collagen turnover biomarkers such as Gal3, PICP and PIIINP are closely related to the presence and extent of LGE and can significantly predict cardiovascular outcome. The joint use of LGE with Gal3 and PICP significantly improved outcome prediction.

Advanced cardiovascular multimodal imaging and aortic stenosis.

Aortic valve stenosis has become the most common valvular heart disease on account of aging population and increasing life expectancy. Echocardiography is the primary diagnosis tool for this, but it still has many flaws. Therefore, advanced cardiovascular multimodal imaging techniques are continuously being developed in order to overcome these limitations. Cardiac magnetic resonance imaging (CMR) allows a comprehensive morphological and functional evaluation of the aortic valve and provides important data for the diagnosis and risk stratification in patients with aortic stenosis. CMR can functionally assess the aortic flow using two-dimensional and time-resolved three-dimensional velocity-encoded phase-contrast techniques. Furthermore, by late gadolinium enhancement and T1-mapping, CMR can reveal the presence of both irreversible replacement and diffuse interstitial myocardial fibrosis. Moreover, its role in guiding aortic valve replacement procedures is beginning to take shape. Recent studies have rendered the importance of active and passive biomechanics in risk stratification and prognosis prediction in patients with aortic stenosis, but more work is required is just in its infancy, but data are promising. In addition, cardiac computed tomography is particularly useful for the diagnosis of aortic valve stenosis, and in preprocedural evaluation of the aorta, while positron emission tomography can be also used to assess valvular inflammation and active calcification. The purpose of this review is to provide a comprehensive overview of current available data regarding advanced cardiovascular multimodal imaging in aortic stenosis.

Left Atrial Geometry and Phasic Function Determined by Cardiac Magnetic Resonance Are Independent Predictors for Outcome in Non-Ischaemic Dilated Cardiomyopathy.

Left atrial (LA) geometry and phasic functions are frequently impaired in non-ischaemic dilated cardiomyopathy (NIDCM). Cardiac magnetic resonance (CMR) can accurately measure LA function and geometry parameters. We sought to investigate their prognostic role in patients with NIDCM. We prospectively examined 212 patients with NIDCM (49 ± 14.2-year-old; 73.5% males) and 106 healthy controls. LA volumes, phasic functions, geometry, and fibrosis were determined using CMR. A composite outcome (cardiac death, ventricular tachyarrhythmias, heart failure hospitalization) was ascertained over a median of 26 months. LA phasic functions, sphericity index (LASI) and late gadolinium enhancement (LA-LGE) were considerably impaired in the diseased group (p < 0.001) and significantly correlated with impaired LV function parameters (p < 0.0001). After multivariate analysis, LA volumes, LASI, LA total strain (LA-εt) and LA-LGE were associated with increased risk of composite outcome (p < 0.001). Kaplan-Meier analysis showed significantly higher risk of composite endpoint for LA volumes (all p < 0.01), LASI > 0.725 (p < 0.003), and LA-εt < 30% (p < 0.0001). Stepwise Cox proportional-hazards models demonstrated a considerable incremental predictive value which resulted by adding LASI to LA-εt (Chi-square = 10.2, p < 0.001), and afterwards LA-LGE (Chi-Square = 15.8; p < 0.0001). NIDCM patients with defective LA volumes, LASI, LA-LGE and LA-εt had a higher risk for an outcome. LA-εt, LASI and LA-LGE provided independent incremental predictive value for outcome.

Cardiotoxicity in HER2-positive breast cancer patients.

Due to the recent advances in diagnosis and management of patients with HER2-positive breast cancer, especially through novel HER2-targeted agents, cardiotoxicity becomes an emerging problem. Although chemotherapy significantly increases survival, the risk of cardiovascular disease development is high and still underestimated and could imply treatment discontinuation. Frequently, due to lack of rigorous diagnosis strategies, cardiotoxicity assessment is delayed, and, moreover, the efficacy of current therapy options in restoring heart function is questionable. For a comprehensive risk assessment, it is vital to characterize the clinical spectrum of HER2-targeted agents and anthracyclines, as well as their pathogenic pathways involved in cardiotoxicity. Advanced cardiovascular multimodal imaging and circulating biomarkers plays primary roles in early assessing cardiotoxicity and also in guiding specific preventive measures. Even though the knowledge in this field is rapidly expanding, there are still questions that arise regarding the optimal approach in terms of timing and methods. The aim of the current review aims to providean overview of currently available data.

Non-ischemic dilated cardiomyopathy and cardiac fibrosis.

Cardiac fibrosis is associated with non-ischemic dilated cardiomyopathy, increasing its morbidity and mortality. Cardiac fibroblast is the keystone of fibrogenesis, being activated by numerous cellular and humoral factors. Macrophages, CD4+ and CD8+ T cells, mast cells, and endothelial cells stimulate fibrogenesis directly by activating cardiac fibroblasts and indirectly by synthetizing various profibrotic molecules. The synthesis of type 1 and type 3 collagen, fibronectin, and α-smooth muscle actin is rendered by various mechanisms like transforming growth factor-beta/small mothers against decapentaplegic pathway, renin angiotensin system, and estrogens, which in turn alter the extracellular matrix. Investigating the underlying mechanisms will allow the development of diagnostic and prognostic tools and discover novel specific therapies. Serum biomarkers aid in the diagnosis and tracking of cardiac fibrosis progression. The diagnostic gold standard is cardiac magnetic resonance with gadolinium administration that allows quantification of cardiac fibrosis either by late gadolinium enhancement assessment or by T1 mapping. Therefore, the goal is to stop and even reverse cardiac fibrosis by developing specific therapies that directly target fibrogenesis, in addition to the drugs used to treat heart failure. Cardiac resynchronization therapy had shown to revert myocardial remodeling and to reduce cardiac fibrosis. The purpose of this review is to provide an overview of currently available data.

Left Ventricular Geometry and Replacement Fibrosis Detected by cMRI Are Associated with Major Adverse Cardiovascular Events in Nonischemic Dilated Cardiomyopathy.

To investigate the relationship between left ventricular (LV) long-axis strain (LAS) and LV sphericity index (LVSI) and outcomes in patients with nonischemic dilated cardiomyopathy (NIDCM) and myocardial replacement fibrosis confirmed by late gadolinium enhancement (LGE) using cardiac magnetic resonance imaging (cMRI), we conducted a prospective study on 178 patients (48 ± 14.4 years; 25.2% women) with first NIDCM diagnosis. The evaluation protocol included ECG monitoring, echocardiography and cMRI. LAS and LVSI were cMRI-determined. Major adverse cardiovascular events (MACEs) were defined as a composite outcome including heart failure (HF), ventricular arrhythmias (VAs) and sudden cardiac death (SCD). After a median follow-up of 17 months, patients with LGE+ had increased risk of MACEs. Kaplan-Meier curves showed significantly higher rate of MACEs in patients with LGE+ (p < 0.001), increased LVSI (p < 0.01) and decreased LAS (p < 0.001). In Cox analysis, LAS (HR = 1.32, 95%CI (1.54-9.14), p = 0.001), LVSI [HR = 1.17, 95%CI (1.45-7.19), p < 0.01] and LGE+ (HR = 1.77, 95%CI (2.79-12.51), p < 0.0001) were independent predictors for MACEs. In a 4-point risk scoring system based on LV ejection fraction (LVEF) < 30%, LGE+, LAS > -7.8% and LVSI > 0.48%, patients with 3 and 4 points had a significantly higher risk for MACEs. LAS and LVSI are independent predictors of MACEs and provide incremental value beyond LVEF and LGE+ in patients with NIDCM and myocardial fibrosis.

Pentraxin-3 and endothelial dysfunction.

Pentraxin 3 (PTX3) is involved in vascular inflammation and endothelial dysfunction through various mechanisms. Until now, most studies confirmed an important link between PTX3 and endothelial dysfunction and identified several pathogenetic pathways. PTX3 modulates inflammatory cells, thus stimulating vascular inflammation. Within endothelial cells, it decreases nitric oxide (NO) synthesis, inhibits cell proliferation and alters their functions. PTX3 blocks the effect of fibroblast growth factor 2 (FGF2) by making a molecular complex with these molecules inactivating them. However, there are substances like the tumor necrosis factor-inducible gene 6 protein (TSG-6) that block the PTX3-FGF2 interaction. Interacting with P-selectin, it promotes vascular inflammatory response and endothelial dysfunction. PTX3 also increases the matrix metalloproteinases synthesis directly or by blocking NO synthesis. From a clinical point of view, PTX3 positively correlates with arterial hypertension, flow mediated dilation and, with intima media thickness. Therefore, the involvement of PTX3 in the pathogenesis and evaluation of endothelial dysfunction is clear, and it may become a biomarker in this direction, but further studies are needed to determine its reliability in this direction. Last but not least, PTX3 could become an effective therapeutic target for preventing this dysfunction, but further research needs to be conducted.