Impaired left ventricular deformation and ventricular-arterial coupling in post-COVID-19: association with autonomic dysregulation.

Coronavirus disease-19 (COVID-19) has extended implications namely the long COVID-19 syndrome. We assessed over-time changes in left ventricular (LV) function, aortic stiffness, autonomic function, and ventricular-arterial coupling (VAC) in post-COVID-19 patients. We followed 34 post-COVID-19 subjects, up to 6 months post-hospital discharge. Subjects without COVID-19 served as control. We evaluated LV global longitudinal strain (LV-GLS), arterial stiffness [carotid-femoral pulse wave velocity (cf-PWV)], and heart rate variability -standard deviation of normal RR intervals (SDNN). VAC was estimated as the ratio of cf-PWV to LV-GLS. Post-COVID-19 individuals (1-month post-hospital discharge) presented with impaired LV-GLS [-18.4%(3.1) vs. -22.0%(2.7), P < 0.001], cf-PWV [12.1 m/s (3.2) vs. 9.6 m/s (1.9), P < 0.001], SDNN [111.3 ms (22.6) vs. 147.2 ms (14.0), P < 0.001], and VAC [-0.68 (0.22) vs. -0.44 (0.10), P < 0.001] compared to control. LV-GLS, SDNN, and VAC improved at the 6-month follow-up however they did not reach control levels. In post-COVID-19 subjects, SDNN and VAC were correlated at the 1-month (R = 0.499, P = 0.003) and 6-month (R = 0.372, P = 0.04) follow-up. Long COVID-19 syndrome was associated with impaired LV-GLS, SDNN, and VAC. Post-COVID-19 subjects presented with autonomic dysregulation associated with aortic stiffness, ventricular-arterial impairment, and LV dysfunction, even 6-months post-hospital discharge. These abnormalities may be related to the presence of long COVID-19 syndrome.

Non-Alcoholic Fatty Liver Disease and Echocardiographic Parameters of Left Ventricular Diastolic Function: A Systematic Review and Meta-Analysis.

The cardiovascular implications of non-alcoholic fatty liver disease (NAFLD) have been associated with heart failure with preserved ejection fraction (HFpEF). The purpose of this review was to conduct a bibliographic search regarding the correlation between NAFLD and the echocardiographic parameters of left ventricular diastolic function. A systematic literature search was conducted in PubMed and Embase for original research data reporting on the association of NAFLD with diastolic function markers [E/e', left atrial volume index (LAVi), left ventricular mass index (LVMi)]. Meta-analysis was performed using the meta and dmetar packages in R studio v.1.4.1106, with p < 0.05 values being considered significant. Results are expressed as the standardized mean difference (SMD) for continuous variables and as the odds ratio (OR) for categorical variables, with respective 95% confidence intervals (CI). Heterogeneity between studies was expressed with index Ι2. From the preliminary search, 2619 articles were found from which 31 studies were included in the final statistical analysis. The meta-analysis of 8 studies which reported on the prevalence of diastolic dysfunction showed that it was increased in patients with NAFLD (OR: 2.07, 95% CI 1.24-3.44 with p = 0.01, I2: 80% with p < 0.01). The meta-analysis of 21 studies showed significantly higher E/e' in NAFLD patients (SMD 1.02, 95% CI 0.43-1.61 with p < 0.001, I2: 97% with p < 0.001). Individuals with NAFLD had increased LAVi (SMD: 0.87, 95% CI 0.38-1.37 with p < 0.001, I2: 96% with p < 0.001) and LVMi (SMD: 0.89, 95% CI 0.31-1.48 with p = 0.003, I2: 100% with p < 0.001). To conclude, in the meta-analysis of 31 observational studies, NAFLD patients were found to have affected left ventricular diastolic function, supporting the hypothesis of NAFLD being associated with HFpEF.

Expression of Circulating miR-21 and -29 and their Association with Myocardial Fibrosis in Hypertrophic Cardiomyopathy.

BACKGROUND: Hypertrophic Cardiomyopathy (HCM) is characterized by myocardial hypertrophy, fibrosis, and sarcomeric disarray. OBJECTIVE: To evaluate the expression levels of circulating miR-21 and -29 in patients with HCM and their association with clinical characteristics and myocardial fibrosis. METHODS: In this case-control study, 27 subjects with HCM, 13 subjects with hypertensive cardiomyopathy, and 10 control subjects were enrolled. Evaluation of patients' functional capacity was made by the six-minute walk test. Echocardiographic measurements of left ventricle systolic and diastolic function were conducted. Cardiac magnetic resonance late gadolinium enhancement (LGE) -through a semiquantitative evaluation- was used in the assessment of myocardial fibrosis extent in HCM patients. The expression of miR-21 and -29 in peripheral blood samples of all patients was measured via the method of quantitative reverse transcription polymerase chain reaction. RESULTS: Circulating levels of miR-21 were higher in both hypertensive and HCM (p<0.001) compared to controls, while expression of miR-29 did not differ between the three studied groups. In patients with HCM and LGE-detected myocardial fibrosis in more than 4 out of 17 myocardial segments, delta CT miR-21 values were lower than in patients with myocardial LGE in 3 or fewer myocardial segments (2.71 ± 1.06 deltaCT vs. 3.50 ± 0.55 deltaCT, p=0.04), indicating the higher expression of circulating miR-21 in patients with more extensive myocardial fibrosis. CONCLUSION: MiR-21 was overexpressed in patients with HCM and hypertensive cardiomyopathy. Importantly, in patients with HCM, more extensive myocardial fibrosis was associated with higher levels of miR-21.

Antithrombotic Treatment in Coronary Artery Disease.

Coronary artery disease exhibits growing mortality and morbidity worldwide despite the advances in pharmacotherapy and coronary intervention. Coronary artery disease is classified in the acute coronary syndromes and chronic coronary syndromes according to the most recent guidelines of the European Society of Cardiology. Antithrombotic treatment is the cornerstone of therapy in coronary artery disease due to the involvement of atherothrombosis in the pathophysiology of the disease. Administration of antiplatelet agents, anticoagulants and fibrinolytics reduce ischemic risk, which is amplified early post-acute coronary syndromes or post percutaneous coronary intervention; though, antithrombotic treatment increases the risk for bleeding. The balance between ischemic and bleeding risk is difficult to achieve and is affected by patient characteristics, procedural parameters, concomitant medications and pharmacologic characteristics of the antithrombotic agents. Several pharmacological strategies have been evaluated in patients with coronary artery disease, such as the effectiveness and safety of antithrombotic agents, optimal dual antiplatelet treatment schemes and duration, aspirin de-escalation strategies of dual antiplatelet regimens, dual inhibition pathway strategies as well as triple antithrombotic therapy. Future studies are needed in order to investigate the gaps in our knowledge, including special populations.

Diabetes Mellitus in Acute Coronary Syndrome.

The global prevalence of diabetes mellitus (DM) has led to a pandemic, with significant microvascular and macrovascular complications including coronary artery disease (CAD), which worsen clinical outcomes and cardiovascular prognosis. Patients with both acute coronary syndrome (ACS) and DM have worse prognosis and several pathophysiologic mechanisms have been implicated including, insulin resistance, hyperglycemia, endothelial dysfunction, platelet activation and aggregations as well as plaque characteristics and extent of coronary lesions. Therefore, regarding reperfusion strategies in the more complex anatomies coronary artery bypass surgery may be the preferred therapeutic strategy over percutaneous coronary intervention while both hyperglycemia and hypoglycemia should be avoided with closed monitoring of glycemic status during the acute phase of myocardial infraction. However, the best treatment strategy remains undefined. Non-insulin therapies, due to the low risk of hypoglycemia concurrently with the multifactorial CV protective effects, may be proved to be the best treatment option in the future. Nevertheless, evidence for the beneficial effects of glucagon like peptide-1 receptor agonists, dipeptidyl-peptidase 4 inhibitors and sodium glycose cotransporter 2 inhibitors, despite accumulating, is not robust and future randomized control trials may provide more definitive data.

The Role of Ranolazine in Heart Failure-Current Concepts.

Heart failure is a complex clinical syndrome with a detrimental impact on mortality and morbidity. Energy substrate utilization and myocardial ion channel regulation have gained research interest especially after the introduction of sodium-glucose co-transporter 2 inhibitors in the treatment of heart failure. Ranolazine or N-(2,6-dimethylphenyl)-2-(4-[2-hydroxy-3-(2-methoxyphenoxy) propyl] piperazin-1-yl) acetamide hydrochloride is an active piperazine derivative which inhibits late sodium current thus minimizing calcium overload in the ischemic cardiomyocytes. Ranolazine also prevents fatty acid oxidation and favors glycose utilization ameliorating the "energy starvation" of the failing heart. Heart failure with preserved ejection fraction is characterized by diastolic impairment; according to the literature ranolazine could be beneficial in the management of increased left ventricular end-diastolic pressure, right ventricular systolic dysfunction and wall shear stress which is reflected by the high natriuretic peptides. Fewer data is evident regarding the effects of ranolazine in heart failure with reduced ejection fraction and mainly support the control of the sodium-calcium exchanger and function of sarcoendoplasmic reticulum calcium adenosine triphosphatase. Ranolazine's therapeutic mechanisms in myocardial ion channels and energy utilization are documented in patients with chronic coronary syndromes. Nevertheless, ranolazine might have a broader effect in the therapy of heart failure and further mechanistic research is required.

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.

Interleukin-1 in Coronary Artery Disease.

Cardiovascular disease is the leading cause of mortality worldwide. Inflammation has long been established as a key component in the pathophysiology of coronary artery disease. The interleukin-1 family consists of 11 members that regulate the inflammatory response through both pro- and anti-inflammatory properties with the Nod-like receptor (NLR) family pyrin domain containing 3 inflammasome having a pivotal role in the process of converting interleukin-1 beta and interleukin- 18, two key inflammatory mediators, into their mature forms. Interleukin-1 affects various cell types that participate in the pathogenesis of atherosclerosis as it enhances the expression of leukocyte adhesion molecules on the surface of endothelial cells and augments the permeability of the endothelial cell barrier, attracting monocytes and macrophages into the vessel wall and aids the migration of smooth muscle cells toward atheroma. It also enhances the aggregation of low-density lipoprotein particles in endothelium and smooth muscle cells and exhibits procoagulant activity by inducing synthesis, cell-surface expression and release of tissue factor in endothelial cells, promoting platelet adhesion. The value of interleukin-1 as a diagnostic biomarker is currently limited, but interleukin-1 beta, interleukin-18 and interleukin-37 have shown promising data regarding their prognostic value in coronary artery disease. Importantly, target anti-inflammatory treatments have shown promising results regarding atherosclerosis progression and cardiovascular events. In this review article, we focus on the immense role of interleukin-1 in atherosclerosis progression, inflammation cascade and in the clinical application of target anti-inflammatory treatments.

Current Concepts and Future Applications of Non-Invasive Functional and Anatomical Evaluation of Coronary Artery Disease.

Over the last decades, significant advances have been achieved in the treatment of coronary artery disease (CAD). Proper non-invasive diagnosis and appropriate management based on functional information and the extension of ischemia or viability remain the cornerstone in the fight against adverse CAD events. Stress echocardiography and single photon emission computed tomography are often used for the evaluation of ischemia. Advancements in non-invasive imaging modalities such as computed tomography (CT) coronary angiography and cardiac magnetic resonance imaging (MRI) have not only allowed non-invasive imaging of coronary artery lumen but also provide additional functional information. Other characteristics regarding the plaque morphology can be further evaluated with the latest modalities achieving a morpho-functional evaluation of CAD. Advances in the utilization of positron emission tomography (PET), as well as software advancements especially regarding cardiac CT, may provide additional prognostic information to a more evidence-based treatment decision. Since the armamentarium on non-invasive imaging modalities has evolved, the knowledge of the capabilities and limitations of each imaging modality should be evaluated in a case-by-case basis to achieve the best diagnosis and treatment decision. In this review article, we present the most recent advances in the noninvasive anatomical and functional evaluation of CAD.

Antithrombotic therapy in TAVI.

Transcatheter aortic valve implantation (TAVI) carries a significant thromboembolic and concomitant bleeding risk, not only during the procedure but also during the periprocedural period. Many issues concerning optimal antithrombotic therapy after TAVI are still under debate. In the present review, we aimed to identify all relevant studies evaluating antithrombotic therapeutic strategies in relation to clinical outcomes after the procedure. Four randomized control trials (RCT) were identified analyzing the post-TAVI antithrombotic strategy with all of them utilizing aspirin lifelong plus clopidogrel for 3-6 months. Seventeen registries have been identified, with a wide variance among them regarding baseline characteristics, while concerning antiplatelet therapy, clopidogrel duration was ranging from 3-12 months. Four non-randomized trials were identified, comparing single vs. dual antiplatelet therapy after TAVI, in respect of investigating thromboembolic outcome events over bleeding complications. Finally, limited data from a single RCT and a retrospective study exist with regards to anticoagulant treatment during the procedure and the optimal antithrombotic therapy when concomitant atrial fibrillation. In conclusion, due to the high risk and frailty of the treated population, antithrombotic therapy after TAVI should be carefully evaluated. Diminishing ischaemic and bleeding complications remains the main challenge in these patients with further studies to be needed in this field.

Antiplatelet and Anticoagulation Therapy in Structural Heart Disease Interventions Beyond TAVI.

Transcatheter interventions for structural heart disease represent an emerging field in interventional cardiology. Undoubtedly, there is an absolute necessity for antiplatelet and/or anticoagulation treatment prior, during and post such interventions. However, currently administered regimens are mainly based in expert consensus recommendations. In the present review we aim to summarize data regarding anti platelet and/or anticoagulation treatment in the following transcatheter structural heart interventions: left atrial appendage closure, atrial septal defect closure, patent foramen oval closure, paravalvular leak closure.

Impact of atherosclerotic plaque components and their distribution on stent deployment: an intravascular-ultrasound virtual histology observational study.

BACKGROUND: The aim of this study was to evaluate how the spatial distribution of each plaque element, defined by intravascular-ultrasound virtual histology (IVUS-VH), may affect stent deployment even at high inflation pressures. METHODS: Thirty-two patients undergoing direct percutaneous coronary intervention and IVUS were evaluated. Fifty-two lesions were treated with drug-eluting stents. Pre-stenting lumen area and real (Rcssla) and average cross-sectional stent lumen area (Acssla) were measured along the whole lesion. Ideal cross-sectional stent lumen area (Icssla) was calculated. Plaque composition was characterized by IVUS-VH. The spatial distribution of each plaque element was quantified by a novel image analysis tool measuring the area and percentage of each plaque component that was adjacent to the lumen. Average stent deployment was defined as: [1 - (Icssla-Acssla)/Icssla]×100%. RESULTS: Stent expansion was significantly less at the site of maximum calcification compared to the average stent deployment (80±9% vs. 85±13%, P=0.044, respectively). Furthermore, wherever calcium was adjacent to the lumen, stent expansion was impaired compared to sites where calcium was non-luminal (70±23% vs. 80±9%, P=0.01, respectively). In contrast, at the site of maximum necrotic core, stent deployment showed a trend to be less compromised, compared to the average stent deployment. CONCLUSIONS: An interaction was found between plaque components and their distribution and stent deployment even at high inflation pressures.

Correlation of CoreValve implantation 'true cover index' with short and mid-term aortic regurgitation: A novel index.

BACKGROUND: 'Cover index' has been proposed to appraise the congruence between the aortic annulus and the device, with the assumption of not taking into account the actual device implantation depth. The aim of this study was to investigate whether the annulus-prosthesis mismatch, as expressed with the new proposed 'true cover index' according to actual implantation depth, can predict aortic regurgitation (AR) after transcatheter aortic valve implantation (TAVI). METHODS: Patients who had undergone TAVI with the self-expandable CoreValve device, were retrospectively studied. All available prosthesis sizes were ex-vivo scanned and the precise diameter at 0.3mm intervals along each device was measured. The 'true cover index' was evaluated, as a ratio of the following: 100×([prosthesis actual diameter at implantation depth-annulus diameter]/prosthesis actual diameter at implantation depth). AR was echocardiographically evaluated at discharge and 30days and classified as prominent if moderate, or trivial if none or mild. RESULTS: Overall, 120 patients who had undergone TAVI, were considered eligible for the study. 'True cover index' was statistically significantly lower among patients with prominent AR in comparison with trivial AR at discharge (5.7±4.8mm vs 9±5.1, p=0.025), as well as at one month post-TAVI (5.4±5.1mm vs 9.0±5.1, p=0.023), indicating increased AR for smaller index. After adjustment for severe annulus calcification, impaired baseline LVEF and previous valvuloplasty, it remained an independent predictor of one month prominent AR (OR: 0.854, CI: 0.730-0.999; p=0.048). 'True cover index' of <4.3 was shown to predict one-month prominent AR with sensitivity =75% and specificity =82.5%. CONCLUSIONS: 'True cover index' is strongly and independently correlated with the short and mid-term AR after CoreValve implantation.

Quantification of new structural features of coronary plaques by computational post-hoc analysis of virtual histology-intravascular ultrasound images.

Cardiovascular disease and complications are often mediated by the development and rupture of atherosclerotic plaques. Plaque composition is a major factor that determines plaque vulnerability. Intravascular ultrasound (IVUS) and spectral analysis of the radio frequency signal provide an in vivo tissue characterisation of atherosclerotic plaques, known as virtual histology (VH-IVUS). In VH-IVUS analysis, four histological tissue components are classified: fibrous, fibro/fatty, necrotic core and calcium. Existing technology determines only the area of each component within the plaque. Quantitative, objective characterisation of other plaque components' patterns within the plaque is lacking. The aim of this study was to determine new compositional and structural indices which indicate spatial distribution, heterogeneity and dispersity of each VH-IVUS-derived component within the plaque area and also with respect to the plaque-lumen border. We developed an automated computational system in Java for the analysis of both single cross-sectional segments and the whole length of the examined plaque (volumetric analysis). The following parameters were computed: the number of different solid segments and the area of the largest solid segment of each component within the plaque, the per cent of the lumen border that is surrounded by each component, the number of different solid segments and the largest area of a solid segment of each component that adjoins the lumen border. Especially components' localisation in relation to the lumen border may significantly influence plaque vulnerability and plaque-stent interaction, which should be investigated in future clinical studies.

Coronary rupture after stent deployment in a patient under chronic immunosuppressive therapy.

Coronary rupture during cardiac catheterization and angioplasty is an uncommon but serious complication. Predisposing factors to this dreadful complication are not well defined. We present a case of coronary artery rupture during an urgent percutaneous intervention in a patient under chronic immunosuppressive therapy with corticosteroids and azathioprine, despite intravascular ultrasound (IVUS) guidance. Initially, the perforation was successfully managed with balloon inflation and finally, a covered stent was deployed at the site. The unexpected rupture, despite optimal IVUS sizing, indicates a possible role of immunosuppressive therapy in coronary artery wall vulnerability. Extra caution should be exerted in such patients while performing coronary interventions and using intracoronary devices.