Acute exercise-induced inflammatory and thrombotic response in hypertensive patients.

PURPOSE: Vigorous physical activity may acutely trigger the onset of an acute coronary syndrome especially in sedentary persons with established cardiovascular risk factors such as arterial hypertension. The rupture of an inflamed coronary plaque and the activation of the coagulation cascade are the main underlying mechanisms. The present study aimed to determine the effect of acute exercise on the inflammatory and thrombotic response in patients with arterial hypertension as compared to normotensive peers. METHODS: After excluding patients with any inflammatory or/and coronary artery disease, a total of 60 non-treated hypertensive patients and 65 normotensive individuals underwent a maximal treadmill exercise testing. Βlood samples were drawn at rest and immediately after peak exercise. High-sensitivity C-reactive protein (hsCRP), serum amyloid A (SAA), white blood cell (WBC), interleukin-6 (IL-6), and total fibrinogen (TF) levels, as well as plasminogen activator inhibitor-1 (PAI-1) activity, were measured. RESULTS: All biomarkers increased with exercise, except PAI-1, which decreased (P < 0.05 for the change between resting and peak exercise for all biomarkers). Αfter adjusting for relevant confounders (duration of exercise, metabolic equivalents, systolic BP, and rate-pressure product achieved at peak exercise), the normotensive group had less marked (P < 0.05) exercise-induced changes than the hypertensive group in hsCRP (7.7 vs. 8.6%), SAA (5.6 vs. 11.9%), WBC (45.0 vs. 51.7%), and PAI-1 (-17.3 vs. -20.1%) and a similar (P = NS) change in IL-6 (23.8 vs. 23.0%) and TF (8.5 vs. 8.5%). CONCLUSION: In conclusion, the acute exercise-induced inflammatory and thrombotic response seems to be more pronounced in non-treated hypertensive patients than in normotensive controls. Possible clinical implications of this finding merit further examination.

Perivascular Fat: A Novel Risk Factor for Coronary Artery Disease.

Perivascular adipose tissue (PVAT) interacts with the vascular wall and secretes bioactive factors which regulate vascular wall physiology. Vice versa, vascular wall inflammation affects the adjacent PVAT via paracrine signals, which induce cachexia-type morphological changes in perivascular fat. These changes can be quantified in pericoronary adipose tissue (PCAT), as an increase in PCAT attenuation in coronary computed tomography angiography images. Fat attenuation index (FAI), a novel imaging biomarker, measures PCAT attenuation around coronary artery segments and is associated with coronary artery disease presence, progression, and plaque instability. Beyond its diagnostic capacity, PCAT attenuation can also ameliorate cardiac risk stratification, thus representing an innovative prognostic biomarker of cardiovascular disease (CVD). However, technical, biological, and anatomical factors are weakly related to PCAT attenuation and cause variation in its measurement. Thus, to integrate FAI, a research tool, into clinical practice, a medical device has been designed to provide FAI values standardized for these factors. In this review, we discuss the interplay of PVAT with the vascular wall, the diagnostic and prognostic value of PCAT attenuation, and its integration as a CVD risk marker in clinical practice.

New Therapeutic Advances in the Management of Tricuspid Valve Regurgitation.

Tricuspid regurgitation (TR) is an intricate disorder that has a negative outlook, while surgical treatment is linked to increased mortality. Primary TR occurs due to a structural defect in the tricuspid valve (TV), while secondary TR is a more prevalent condition often associated with pulmonary hypertension, heart failure, and atrial fibrillation. The use of specific surgical procedures to improve TR is limited in everyday clinical practice due to the heightened surgical risk and delayed patient presentation. The development of other transcatheter heart valve procedures has led to a significant increase in transcatheter TV operations, which can be attributed to certain technological advancements. This review aims to provide an updated overview of transcatheter TV procedures, available alternative therapies, and standards for patient selection. It will also highlight the current state of development in this field, which is characterized by rapid progress and numerous ongoing clinical trials.

Emerging Transcatheter Therapies for Valvular Heart Disease: Focus on Mitral and Tricuspid Valve Procedures.

The emergence of percutaneous treatment options provides novel therapeutic alternatives for older and feeble patients who are at high risk for any surgical procedure. The purpose of our review was to offer an up-to-date analysis of the rapidly expanding field of percutaneous technologies for mitral, tricuspid, and pulmonary procedures. Edge-to-edge repair is an established treatment for secondary mitral regurgitation (MR), while transcatheter mitral valve replacement is a potential and expanding option for managing both secondary and primary MR. However, additional advancements are necessary to enhance the safety and feasibility of this procedure. Transcatheter tricuspid intervention is an emerging option that was conceived after the success of transcatheter procedures in aortic and mitral valves, and it is currently still in the early stages of advancement. This can be attributed, at least in part, to the previously overlooked effect of tricuspid regurgitation on patient outcomes. The development of edge-to-edge repair represents the forefront of innovations in transcatheter procedures. There is a scarcity of data about tricuspid annuloplasty and replacement, and further study is necessary. Transcatheter mitral, tricuspid, and pulmonary procedures show prospects for the future, while their role in clinical practice has not been definitively established.

Long-Term Outcomes of Aortic Stenosis Patients with Different Flow/Gradient Patterns Undergoing Transcatheter Aortic Valve Implantation.

Background: Few data exist on the comparative long-term outcomes of severe aortic stenosis (AS) patients with different flow-gradient patterns undergoing transcatheter aortic valve implantation (TAVI). This study sought to evaluate the impact of the pre-TAVI flow-gradient pattern on long-term clinical outcomes after TAVI and assess changes in the left ventricular ejection fraction (LVEF) of different subtypes of AS patients following TAVI. Methods: Consecutive patients with severe AS undergoing TAVI in our institution were screened and prospectively enrolled. Patients were divided into four subgroups according to pre-TAVI flow/gradient pattern: (i) low flow-low gradient (LF-LG): stroke volume indexed (SVi) ≤ 35 mL/m2 and mean gradient (MG) < 40 mmHg); (ii) normal flow-low gradient (NF-LG): SVi > 35 mL/m2 and MG < 40 mmHg; (iii) low flow-high gradient (LF-HG): Svi 35 mL/m2 and MG ≥ 40 mmHg and (iv) normal flow-high gradient (NF-HG): SVi > 35 mL/m2 and MG ≥ 40 mmHg. Transthoracic echocardiography was repeated at 1-year follow-up. Clinical follow-up was obtained at 12 months, and yearly thereafter until 5-year follow-up was complete for all patients. Results: A total of 272 patients with complete echocardiographic and clinical follow-up were included in our analysis. Their mean age was 80 ± 7 years and the majority of patients (N = 138, 50.8%) were women. 62 patients (22.8% of the study population) were distributed in the LF-LG group, 98 patients (36%) were LF-HG patients, 95 patients (34.9%) were NF-HG, and 17 patients (6.3%) were NF-LG. There was a greater prevalence of comorbidities among LF-LG AS patients. One-year all-cause mortality differed significantly between the four subgroups of AS patients (log-rank p: 0.022) and was more prevalent among LF-LG patients (25.8%) compared to LF-HG (11.3%), NF-HG (6.3%) and NF-LG patients (18.8%). At 5-year follow-up, global mortality remained persistently higher among LF-LG patients (64.5%) compared to LF-HG (47.9%), NF-HG (42.9%), and NF-LG patients (58.8%) (log-rank p: 0.029). At multivariable Cox hazard regression analysis, baseline SVi (HR: 0.951, 95% C.I.; 0.918-0.984), the presence of at least moderate tricuspid regurgitation at baseline (HR: 3.091, 95% C.I: 1.645-5.809) and at least moderate paravalvular leak (PVL) post-TAVI (HR: 1.456, 95% C.I.: 1.106-1.792) were significant independent predictors of late global mortality. LF-LG patients and LF-HG patients exhibited a significant increase in LVEF at 1-year follow-up. A lower LVEF (p < 0.001) and a lower Svi (p < 0.001) at baseline were associated with LVEF improvement at 1-year. Conclusions: Patients with LF-LG AS have acceptable 1-year outcomes with significant improvement in LVEF at 1-year follow-up, but exhibit exceedingly high 5-year mortality following TAVI. The presence of low transvalvular flow and at least moderate tricuspid regurgitation at baseline and significant paravalvular leak post-TAVI were associated with poorer long-term outcomes in the entire cohort of AS patients. The presence of a low LVEF or a low SVi predicts LVEF improvement at 1-year.

Direct Oral Anticoagulants use in Patients with Stable Coronary Artery Disease, Acute Coronary Syndrome or Undergoing Percutaneous Coronary Intervention.

The investigation for the optimal anticoagulation strategy for patients with stable coronary artery disease, acute coronary syndromes, and undergoing percutaneous coronary intervention constitutes a great challenge for physicians and is a field of extensive research. Although aspirin is commonly recommended as a protective measure for all patients with coronary artery disease and dual antiplatelet therapy for those undergoing procedures, such as percutaneous coronary intervention or coronary artery bypass graft surgery, the risk of recurrent cardiovascular events remains significant. In this context, the shortcomings associated with the use of vitamin K antagonists have led to the assessment of direct oral anticoagulants as promising alternatives. This review will explore and provide a comprehensive analysis of the existing data regarding the use of direct oral anticoagulants in patients with stable coronary artery disease or acute coronary syndrome, as well as their effectiveness in those undergoing percutaneous coronary intervention or coronary artery bypass graft surgery.

Electro-Mechanical Alterations in Atrial Fibrillation: Structural, Electrical, and Functional Correlates.

Atrial fibrillation is the most common arrhythmia encountered in clinical practice affecting both patients' survival and well-being. Apart from aging, many cardiovascular risk factors may cause structural remodeling of the atrial myocardium leading to atrial fibrillation development. Structural remodelling refers to the development of atrial fibrosis, as well as to alterations in atrial size and cellular ultrastructure. The latter includes myolysis, the development of glycogen accumulation, altered Connexin expression, subcellular changes, and sinus rhythm alterations. The structural remodeling of the atrial myocardium is commonly associated with the presence of interatrial block. On the other hand, prolongation of the interatrial conduction time is encountered when atrial pressure is acutely increased. Electrical correlates of conduction disturbances include alterations in P wave parameters, such as partial or advanced interatrial block, alterations in P wave axis, voltage, area, morphology, or abnormal electrophysiological characteristics, such as alterations in bipolar or unipolar voltage mapping, electrogram fractionation, endo-epicardial asynchrony of the atrial wall, or slower cardiac conduction velocity. Functional correlates of conduction disturbances may incorporate alterations in left atrial diameter, volume, or strain. Echocardiography or cardiac magnetic resonance imaging (MRI) is commonly used to assess these parameters. Finally, the echocardiography-derived total atrial conduction time (PA-TDI duration) may reflect both atrial electrical and structural alterations.

Impact of Evolution of Self-Expandable Aortic Valve Design: Peri-Operative and Short-Term Outcomes.

A few data exist on the differences of implantable aortic valve bio-prostheses. We investigate three generations of self-expandable aortic valves in terms of the outcomes. Patients undergoing transcatheter aortic valve implantation (TAVI) were allocated into three groups according to the valve type: group A (CoreValveTM), group B (EvolutTMR) and group C (EvolutTMPRO). The implantation depth, device success, electrocardiographic parameters, need for permanent pacemaker (PPM), and paravalvular leak (PVL) were assessed. In the study, 129 patients were included. The final implantation depth did not differ among the groups (p = 0.07). CoreValveTM presented greater upward jump of the valve at release (2.88 ± 2.33 mm vs. 1.48 ± 1.09 mm and 1.71 ± 1.35 mm, for groups A, B, and C, respectively, p = 0.011). The device success (at least 98% for all groups, p = 1.00) and PVL rates (67% vs. 58%, vs. 60% for groups A, B, and C, respectively, p = 0.64) did not differ. PPM implantation within 24 h (33% vs. 19% vs. 7% for groups A, B, and C, respectively, p = 0.006) and until discharge (group A: 38% vs. group B: 19% and group C: 9%, p = 0.005) was lower in the newer generation valves. Newer generation valves present better device positioning, more predictable deployment, and fewer rates of PPM implantation. No significant difference in PVL was observed.

Adhesion Molecules as Prognostic Biomarkers in Coronary Artery Disease.

Atherosclerosis is a progressive disease, culminating in the production of atherosclerotic plaques in arteries through intricate pathophysiological processes. The progression of this disorder is based on the effect of triggering factors -mainly hyperlipidemia, diabetes mellitus, arterial hypertension, and smoking- on the endothelium. Coronary artery disease (CAD) is an atherosclerotic disease with a higher prevalence among individuals. Pro- and anti-inflammatory cytokines are the main contributors to atherosclerotic plaque formation. CAD and its manifestations multifactorial affect patients' quality of life, burdening the global healthcare system. Recently, the role of adhesion molecules in CAD progression has been recognized. Physicians delve into the pathophysiologic basis of CAD progression, focusing on the effect of adhesion molecules. They are proteins that mediate cell-cell and cell-extracellular matrix interaction and adhesion, driving the formation of atherosclerotic plaques. Several studies have assessed their role in atherosclerotic disease in small cohorts and in experimental animal models as well. Furthermore, several agents, such as nanoparticles, have been introduced modifying the main atherosclerotic risk factors as well as targeting the endothelial inflammatory response and atherosclerotic plaque stabilization. In this review, we discuss the role of adhesion molecules in atherosclerosis and CAD progression, as well as the potential to be used as targeting moieties for individualized treatment.

Effects of Chemotherapy on Aortic 18-Fluorodeoxyglucose Uptake in Patients With Hodgkin and Non-Hodgkin Lymphoma.

Background: Despite advances in the treatment of oncology patients, therapy-related side effects may lead to premature morbidity. Inflammatory activation that has been linked to cardiovascular disease is crucial for the pathogenesis of both Hodgkin (HL) and non-Hodgkin lymphoma (NHL). Objectives: The purpose of this study was to assess the vascular effects of chemotherapy in patients with HL and NHL by positron emission tomography/computed tomography with 18-fluorodeoxyglucose (18-FDG PET/CT) and to investigate interactions with systemic inflammation as assessed by circulating inflammatory markers. Methods: Between July 2015 and July 2019, 65 consecutive patients (mean age 56 ± 17.78 years) with confirmed diagnosis of either HL (n = 33) or NHL (n = 32) were prospectively studied. PET/CT imaging was performed at baseline, at an interim phase, and after first-line treatment. Aortic FDG uptake was assessed by measuring global aortic target-to-background ratio (GLA-TBR). Serum biomarkers interleukin (IL)-6 and IL-1b were measured at each phase. Results: Patients with HL demonstrated significant reduction in aortic TBR after first-line treatment (median GLA-TBR baseline: 1.98, median GLA-TBR third scan: 1.75, median difference = -0.20, 95% CI: -0.07 to -0.33, P = 0.006), which remained significant after adjustment for confounders (adj. R2 of model = 0.53). In contrast, patients with NHL did not demonstrate a significant aortic inflammation response (P = 0.306). Furthermore, patients with HL demonstrated a significant reduction in IL-6 (P = 0.048) and IL-1b (P = 0.045), whereas patients with NHL did not demonstrate significant reduction in IL-6 (P = 0.085) and IL-1b levels (P = 0.476). Conclusions: Aortic inflammation, as assessed by 18-FDG PET/CT, is reduced in HL patients after first-line treatment but not in NHL patients. These findings imply that different pathophysiological pathways and different therapies might affect the arterial bed in different ways for patients with lymphoma.

Transthoracic ultrasound; seeking the heart in a patient with a large left-sided cirrhotic hydrothorax.

A case of a patient with liver cirrhosis and a large left-sided pleural effusion displacing the heart rightward is presented and the best views to acquire images enabling evaluation of the cardiac function are highlighted. Understanding the modified intrathoracic anatomy in patients with pleural effusions enables quick and focused assessment and can shorten evaluation time while preserving high image quality.

Precision Medicine in Aortic Anastomosis: A Numerical and Experimental Study of a Novel Double-Sided Needle.

BACKGROUND: Hand-sewn anastomosis is a crucial part of aortic reconstruction surgery and significantly affects its outcome. The present study presents a novel, bidirectional surgical needle aimed to improve aortic anastomosis in terms of speed and ease of use. Our objective was to assess the efficacy of the new design in comparison with the conventional needle. METHODS: A series of simulations were conducted with COMSOL software in order to perform a fatigue comparative analysis between the new and the conventional needle design. Ease of penetration into a piece of polydimethylsiloxane was evaluated. Lastly, the prototype was tested under in-vitro conditions in comparison with the conventional needle. RESULTS: Based on fatigue analysis, the new needle design improves durability, provided the two tips are equally used. The polytetrafluoroethylene coating improves penetration into the tissue by 7% to 17%, while electropolishing improves penetration up to 19%. When using the novel needle design, the average anastomotic task completion time was significantly reduced by 22% and the overall distance of hand movements was significantly reduced by 20%. CONCLUSIONS: The proposed design exhibited a shorter anastomotic time and seems promising in relation to ease of use and simplicity of the anastomotic technique it introduces.

Hypertensive crisis and pulmonary edema following rituximab-induced anaphylaxis.

Rituximab is a monoclonal antibody against the protein CD20. Various lymphomas as well as non-malignant immune disorders are treated with this antibody. Hypersensitivity reactions associated with the use of rituximab include urticaria, hypotension, chest tightness, vomiting, oxygen desaturation and bronchospasm. A very uncommon case of hypertensive crisis and pulmonary edema following rituximab-induced hypersensitivity reaction in an 80-year-old man receiving rituximab for non-Hodgkin lymphoma is reported. Anaphylaxis manifesting as coronary vasospasm following drug treatment, including rituximab, could be proved a serious condition in patients who need specific treatment. In these patients desensitization protocols seem to be mandatory.

Contemporary management of pericardial effusion.

Pericardial effusion is a relatively common clinical condition with a variety of clinical manifestations ranging from incidentally discovered asymptomatic cases to life-threatening cardiac tamponade. The etiology encompasses idiopathic cases and forms secondary to different conditions, including autoimmune diseases, malignancies, metabolic disorders, etc. While medical therapy should be offered to patients with elevation of inflammatory markers, in specific forms treatment should be appropriate to the underlying disorder. In cases with hemodynamic compromise pericardial drainage either with pericardiocentesis or pericardial "window" is indicated for therapeutic and diagnostic purposes. In the remainder, factors like comorbidities, size and location of the pericardial effusion will influence the clinical decision making. In asymptomatic or minimally symptomatic chronic large idiopathic pericardial effusions, according to recent evidence, a conservative approach with watchful waiting seems the most reasonable option. The prognosis of pericardial effusions largely depends on the underlying etiologies. Metastatic spread to the pericardium has an ominous prognosis whereas large to moderate effusions have been often associated with known or newly discovered specific underlying causes. Chronic small idiopathic effusions have an excellent prognosis and do not require specific monitoring. Large chronic idiopathic effusions in clinically stable patients require a 3 to 6-month assessment ideally in a specialized unit.

Assessment of arterial baroreflex sensitivity by different computational analyses of pressure wave signals alone.

BACKGROUND AND OBJECTIVE: Baroreflex sensitivity (BRS) is an important indicator of the functionality of the arterial baroreceptors, and its assessment may have major research and clinical implications. An important requirement for its quantification is the continuous recording of electrocardiography (ECG) signal, so as to extract the RR interval, in parallel with continuous beat-to-beat blood pressure recording. We aimed to accurately calculate the RR Interval from pressure wave recordings per se, namely, the Pulse Interval (PI) using various arterial pulse wave analysis algorithms and to evaluate the precision and accuracy of BRS values calculated with the PI compared to BRS values calculated with the RR Interval. METHODS: We analyzed the open access data of the Eurobavar study, which contains a set of ECG and arterial blood pressure (BP) wave signals recorded at 11 European centers. Pressure waveforms were continuously recorded by the Finapres apparatus which uses a finger cuff. The cuff pressure around the finger is dynamically adjusted by a servo-system to equal intra-arterial pressure, thus allowing the continuous recording of beat-to-beat BP waves. RR Interval was calculated from the ECG, whereas, PI was extracted from the arterial pulse waveforms, using 4 different methods (minimum, maximum, maximum 1st derivative and intersecting tangents method). BRS values were estimated by time domain and frequency domain methods. In order to compare agreement, accuracy, precision, variability, and the association between the reference BRS using the RR Interval and the BRS values using PI, standard statistical methods (i.e. intraclass correlation coefficients, RMSE, regression analysis) and Bland-Altman methods were performed. RESULTS: We found that analysis of pressure waves alone by frequency-based (i.e. spectral) methods, provides the most accurate results of BRS estimation compared to time-domain methods (ICC > 0.9, R > 0.9, RMSE > 0.8 ms/mmHg). Concerning the spectral method, any algorithm for PI calculation is sufficient, as all show excellent agreement with the respective RR-intervals determined by ECG time series. Only the intersecting tangents and the maximum 1st derivative methods for PI calculation produce the most accurate results in time domain BRS estimation. CONCLUSION: BRS estimation by proper analysis of pressure wave signals alone is feasible and accurate. Further studies are needed to investigate the clinical validity and relevance of the different BRS estimations in diagnostic, prognostic and therapeutic levels.