The Role of Echocardiography in the Diagnosis and Prognosis of Pulmonary Hypertension.

The right heart catheterisation constitutes the gold standard for pulmonary hypertension (PH) diagnosis. However, echocardiography remains a reliable, non-invasive, inexpensive, convenient, and easily reproducible modality not only for the preliminary screening of PH but also for PH prognosis. The aim of this review is to describe a cluster of echocardiographic parameters for the detection and prognosis of PH and analyse the challenges of echocardiography implementation in patients with suspected or established PH. The most important echocardiographic index is the calculation of pulmonary arterial systolic pressure (PASP) through the tricuspid regurgitation (TR). It has shown high correlation with invasive measurement of pulmonary pressure, but several drawbacks have questioned its accuracy. Besides this, the right ventricular outflow track acceleration time (RVOT-AT) has been proposed for PH diagnosis. A plethora of echocardiographic indices: right atrial area, pericardial effusion, the tricuspid annular plane systolic excursion (TAPSE), the TAPSE/PASP ratio, tricuspid annular systolic velocity (s'), can reflect the severity and prognosis of PH. Recent advances in echocardiography with 3-dimensional right ventricular (RV) ejection fraction, RV free wall strain and right atrial strain may further assist the prognosis of PH.

The diagnostic value of stress echocardiography with limited myocardial ischemia in high-risk patients.

BACKGROUND: The diagnostic value of limited myocardial ischemia in DSE is not well known. OBJECTIVES: We investigated whether myocardial ischemia during dobutamine stress echocardiography (DSE) in 1 apical segment of any of the ventricular walls of the left ventricle relates to the anatomical and functional stenosis of the suppling coronary artery. METHODS: Our observational, prospective study enrolled 212 patients, symptomatic or asymptomatic, with newly diagnosed limited myocardial ischemia on DSE. Almost 25% of them had already known CAD, while the rest were divided into low-risk and high-risk groups, integrating 1-2 and ≥3 classical cardiovascular risk factors, respectively. After DSE, all patients underwent invasive coronary angiography (ICA) and were followed up for one year. In coronary arteries distributing ischemic area, the calculated stenosis ≥50% and FFR<0.8 were considered anatomically and functionally significant, respectively. In the latter cases, the patients underwent coronary revascularization. RESULTS: Significant anatomical and functional stenosis of the supplying coronary artery was common among patients with already known CAD (62.5% and 44.5%, respectively) or those without CAD but a high-risk profile (60.2% and 25.6%, respectively). In logistic regression analysis, CAD revascularization was independently determined by an already known CAD, diabetes mellitus, and high-risk profile. During follow-up, 24 patients experienced ACS or new angina episodes, which were associated with diabetes and smoking in univariate analysis. CONCLUSION: Limited myocardial ischemia may implicate significant anatomical and functional coronary stenosis among individuals with a history of CAD or those without known CAD but a high-risk profile. The prognostic value of our findings requires further investigation.

The Role of Osteopontin in Atherosclerosis and Its Clinical Manifestations (Atherosclerotic Cardiovascular Diseases)-A Narrative Review.

Atherosclerotic cardiovascular diseases (ASCVDs) are the most common and severe public health problem nowadays. Osteopontin (OPN) is a multifunctional glycoprotein highly expressed at atherosclerotic plaque, which has emerged as a potential biomarker of ASCVDs. OPN may act as an inflammatory mediator and/or a vascular calcification (VC) mediator, contributing to atherosclerosis progression and eventual plaque destabilization. In this article, we discuss the complex role of OPN in ASCVD pathophysiology, since many in vitro and in vivo experimental data indicate that OPN contributes to macrophage activation and differentiation, monocyte infiltration, vascular smooth muscle cell (VSMC) migration and proliferation and lipid core formation within atherosclerotic plaques. Most but not all studies reported that OPN may inhibit atherosclerotic plaque calcification, making it "vulnerable". Regarding clinical evidence, serum OPN levels may become a biomarker of coronary artery disease (CAD) presence and severity. Significantly higher OPN levels have been found in patients with acute coronary syndromes than those with stable CAD. In limited studies of patients with peripheral artery disease, circulating OPN concentrations may be predictive of future major adverse cardiovascular events. Overall, the current literature search suggests the contribution of OPN to atherosclerosis development and progression, but more robust evidence is required.

Factors Associated with Extended-Spectrum ß-Lactamases and Carbapenem-Resistant Klebsiella pneumoniae Bloodstream Infections: A Five-Year Retrospective Study.

Klebsiella pneumoniae is one of the leading causes of nosocomial infections. It has been estimated that nosocomial infection by Klebsiella pneumoniae comprises 3-8% of all nosocomial infections. Klebsiella pneumoniae bloodstream infections (BSIs) occur worldwide with varying mortality. Resistant strains, like those producing extended-spectrum beta-lactamases (ESBL) and carbapenemases, are becoming increasingly common, especially in hospital settings, posing therapeutic challenges. In this article, we aimed to study the epidemiology and risk factors of BSIs due to resistant Klebsiella pneumoniae strains in the period 1 January 2014-31 December 2018 at the Nicosia General Hospital, the largest tertiary hospital in Cyprus. Data on demographics, co-morbidities, prior hospitalization, prior intensive care unit (ICU) admission, previous antimicrobial use, nosocomial acquisition of the infection, the presence of a prosthetic device or surgery, and the primary site of infection were retrospectively recorded. Associations between the detection of ESBL Klebsiella pneumoniae BSIs and factors/covariates were examined using logistic regression. This study involved 175 patients with BSI caused by Klebsiella pneumoniae. Of these, 61 BSIs were caused by ESBL strains, 101 by non-ESBL, and 13 by carbapenem-resistant (CR) strains. In univariable analyses, age, sex, heart disease, antimicrobial use during current admission, previous hospitalization (ward or ICU), and primary BSI were associated with the presence of an ESBL strain. Antibiotic use during current admission and heart disease remained statistically significantly associated with ESBL Klebsiella pneumoniae BSI in multivariable models. Antibiotic use during current admission, respiratory infection, and a recent history of surgery were more prevalent among CR Klebsiella pneumoniae BSI patients than among non-CR Klebsiella pneumoniae BSI patients. Our study showed that recent antimicrobial use and heart disease were associated with BSI due to ESBL-producing Klebsiella pneumoniae. This finding could inform clinical practice in hospital settings.

Pulmonary Hypertension in Left Ventricular Valvular Diseases: A Comprehensive Review on Pathophysiology and Prognostic Value.

Left ventricular (LV) valvular diseases, make up one of the most common etiologies for pulmonary hypertension (PH), and it is not well understood how and at which degree it affects prognosis. The aim of the present study was a comprehensive review of the pathophysiologic mechanism of PH in patients with LV valvular diseases and the prognostic value of baseline and post-intervention PH in patients undergoing interventional treatment. The pathophysiology of PH in patients with LV valvular diseases involves gradual elevation of left ventricular filling pressure and left atrial pressure, which are passively transmitted to the pulmonary circulation and raise pulmonary artery systolic pressure (PASP). A long-lasting exposure to elevated PASP progressively leads to initially functional and thereafter irreversible structural changes in the pulmonary vasculature, leading up to high pulmonary vascular resistance. Surgical treatment of severe LV valvular diseases is highly effective in patients without resting PH or those with exercise-induced PH (EIPH) before intervention. In the case of pre-operative PH, successful interventional therapy decreases PASP, but the post-operative cardiac and all-cause mortality remain higher compared to patients without pre-operative PH. Hence, it is of paramount importance to detect patients with severe LV valvulopathies before the development of PH, since they will get greater benefits from early intervention.

Systemic Lupus Erythematosus and Pulmonary Hypertension.

Pulmonary Hypertension (PH) is a common manifestation in patients with Systemic Lupus Erythematosus (SLE) and varies from asymptomatic to life-threatening disease. PH can result not only from immune system dysregulation, but also from various conditions, including cardiorespiratory disorders and thromboembolic diseases. Most commonly, SLE-related PH presents with non-specific symptoms, such as progressive dyspnea on exertion, generalized fatigue and weakness and eventually dyspnea at rest. Prompt diagnosis of SLE-related PH and early identification of the underlying pathogenetic mechanisms is demanded in order to introduce targeted therapy to prevent irreversible pulmonary vascular damage. In most cases the management of PH in SLE patients is similar to idiopathic pulmonary arterial hypertension (PAH). Furthermore, specific diagnostic tools like biomarkers or screening protocols, to establish early diagnosis seem to be not available yet. Although, the survival rates for patients with SLE-related PH vary between studies, it is evident that PH presence negatively affects the survival of SLE patients.

Exercise-Induced Pulmonary Hypertension: A Valid Entity or Another Factor of Confusion?

Exercise-induced pulmonary hypertension EIPH has been defined as an increase in mean pulmonary arterial pressure (mPAP) during exercise in otherwise normal values at rest. EIPH reflects heart and/or lung dysfunction and may precede the development of manifest pulmonary hypertension (PH) in a proportion of patients. It is also associated with decreased life expectancy in patients with heart failure with reduced ejection fraction (HFrEF) or left ventricle (LV) valvular diseases. Diastolic dysfunction exacerbated during exercise relates to increased LV filling pressure and left atrial pressure (LAP). In this context backward, transmitted pressure alone or accompanied with backward blood flow promotes EIPH. The gold standard of EIPH assessment remains the right heart catheterization during exercise, which is an accurate but invasive method. Alternatively, non-invasive diagnostic modalities include exercise stress echocardiography (ESE) and cardiopulmonary exercise testing (CPET). Both diagnostic tests are performed under gradually increasing physical stress using treadmill and ergo-cycling protocols. Escalating workload during the exercise is analogous to the physiological response to real exercise. The results of the latter techniques show good correlation with invasive measurements, but they suffer from lack of validation and cut-off value determination. Although it is not officially recommended, there are accumulated data supporting the importance of EIPH diagnosis in the assessment of other mild/subclinical or probably fatal diseases in patients with latent PH or heart failure or LV valvular disease, respectively. Nevertheless, larger, prospective studies are required to ensure its role in clinical practice.

Potential Pharmaceutical Applications of Quercetin in Cardiovascular Diseases.

Quercetin, as a member of flavonoids, has emerged as a potential therapeutic agent in cardiovascular diseases (CVDs) in recent decades. In this comprehensive literature review, our goal was a critical appraisal of the pathophysiological mechanisms of quercetin in relation to the classical cardiovascular risk factors (e.g., hyperlipidemia), atherosclerosis, etc. We also assessed experimental and clinical data about its potential application in CVDs. Experimental studies including both in vitro methods and in vivo animal models mainly outline the following effects of quercetin: (1) antihypertensive, (2) hypolipidemic, (3) hypoglycemic, (4) anti-atherosclerotic, and (5) cardioprotective (suppressed cardiotoxicity). From the clinical point of view, there are human studies and meta-analyses implicating its beneficial effects on glycemic and lipid parameters. In contrast, other human studies failed to demonstrate consistent favorable effects of quercetin on other cardiometabolic risk factors such as MS, obesity, and hypertension, underlying the need for further investigation. Analyzing the reason of this inconsistency, we identified significant drawbacks in the clinical trials' design, while the absence of pharmacokinetic/pharmacodynamic tests prior to the studies attenuated the power of clinical results. Therefore, additional well-designed preclinical and clinical studies are required to examine the therapeutic mechanisms and clinical efficacy of quercetin in CVDs.

A new approach of statin therapy in carotid atherosclerosis: Targeting indices of plaque vulnerability on the top of lipid-lowering. A narrative review.

Novel imaging techniques and biomarkers have emerged as surrogate markers of carotid plaque vulnerability. In parallel, statin administration in patients with established carotid atherosclerosis not requiring revascularization has reduced the number of consequent cerebrovascular events. This reduction is not only attributed to the lipid-lowering properties of statins but also to their pleiotropic actions. The present literature review aimed to summarize the stabilizing effects of statins on carotid plaques based on imaging modalities and biomarkers and propose an alternative approach to their implementation. Moreover, we assessed the perioperative use of statins in patients undergoing carotid revascularization and the impact of aggressive vs. conventional statin therapy. Recent studies using: (1) ultrasound indices of plaque echogenicity; (2) fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) scans for plaque inflammation assessment; or (3)magnetic resonance imaging (MRI) scans quantifying intraplaque hemorrhage, and lipid-rich necrotic core (LRNC) have shown quite promising results in evaluation of carotid plaque vulnerability. Based on those imaging modalities, a growing number of studies have demonstrated a very modest carotid plaque regression due to/induced by statins, while their stabilizing impact is disproportionally higher. Other studies assaying several biomarkers (e.g. inflammation, etc.) have confirmed a statin-induced carotid plaque stabilization. All the aforementioned benefits followed a dose-dependent pattern of statins, on top of the low-density lipoprotein cholesterol (LDL-C) target in current guidelines. In the case of symptomatic patients with carotid atherosclerosis suitable for revascularization, robust evidence implicates a significant statin-related reduction of perioperative cardiovascular risk only in patients undergoing endarterectomy.

Pityriasis Rosea Induced by COVID-19 Vaccination.

It is increasingly recognized that SARS-CoV-2 infection and COVID-19 vaccines have been associated with skin disorders, including pityriasis rosea. It has been reported that pityriasis rosea has been triggered by several vaccines, as a rare side-effect. We present two cases of COVID-19 vaccine-induced pityriasis rosea. Skin lesions appeared in a 49-year-old female 8 days after the first dose of the BNT162b2 mRNA vaccine and in a 53-year-old male 7 days after the second dose of the same vaccine. The exanthem was self-limited in both patients over a period of a month. LEARNING POINTS: Physicians should be aware that pityriasis rosea is a rare side-effect of COVID-19 vaccination.Pityriasis rosea is self-limiting and no medical treatment is usually required.

The interplay between statins and adipokines. Is this another explanation of statins' 'pleiotropic' effects?

Statin therapy comprises an integral part of secondary and to a lesser extent of primary cardiovascular disease prevention. This is attributed not only to their lipid-lowering properties, but as well to a plethora of pleiotropic actions. Recently, the cytokines secreted by adipose tissue, the so-called adipokines, have been proved to play a critical role in various pathophysiological functions, among which inflammation and atherosclerosis development and vulnerability. The aim of this literature review was to summarize the effects of statins and the underlying mechanisms on the circulating levels of the most common adipokines regulating atherosclerosis process, as a part of their pleiotropic function. Up to now, robust evidence implicates a significant statin-induced reduction of pro-inflammatory adipokines IL-6, TNF-a and visfatin. Weak evidence from limited, small and mostly non-randomized studies suggest increased levels of anti-inflammatory adipokines apelin, vaspin and omentin-1 after statin therapy. In the rest of most known adipokines, statins have shown either controversial (adiponectin, retinol binding protein-4 and fetuin-A) or negligible effects (leptin and resistin) on their circulating levels. Therefore, statins may favourably alter the balance of inflammatory/anti-inflammatory adipokines, implicating a novel atheroprotective mechanism. However, the interplay between statins and adipokines is still not fully elucidated and its potential clinical relevance is warranted.

Comparative virulence of seasonal viruses responsible for lower respiratory tract infections: a southern European multi-centre cohort study of hospital admissions.

OBJECTIVES: Our study aimed to compare the clinical severity of lower respiratory tract infections (LRTI's) caused by Influenza and Respiratory Syncytial Virus (RSV). METHODS: We conducted a retrospective cohort study of LRTI admissions with positive PCR results for Influenza or RSV from 2017 to 2019 in three teaching hospitals in southern Europe. Data on clinical characteristics, viral agents and disease outcome were collected. Nosocomial infection was excluded. Main outcomes were invasive mechanical ventilation and in-hospital death. RESULTS: A total of 984 patients were included. Median age was 75 years. Influenza A was the most frequently identified virus (56.5%), of which 27.1% were subtype H1N1 and 53.0% H3N2. Influenza B was isolated in 22.3% and RSV in 21.0%. There were 10.5% of patients who died during admission and 8.3% submitted to IMV. Influenza A H1N1 was associated with lower age and less co-morbidity, while the opposite was observed for RSV. Influenza A H1N1 was independently associated with both higher risk of death (adjusted odds ratio 2.0 [1.2-3.4] p = 0.008) and IMV (adjusted odds ratio 5.1 [3.0-8.5] p < 0.001). CONCLUSION: Influenza A H1N1 was an independent predictor of mortality and IMV. These findings may have implications on hospital resource planning and vaccination policies.

Influenza and respiratory syncytial virus infections in the oldest-old continent.

SARS-CoV-2 dramatically revealed the sudden impact of respiratory viruses in our lives. Influenza and respiratory syncytial virus (RSV) infections are associated with high rates of morbidity, mortality, and an important burden on healthcare systems worldwide, especially in elderly patients. The aim of this study was to identify severity predictors in the oldest-old admitted with influenza and/or RSV infections. This is a multicenter, retrospective study of all oldest-old patients (≥ 85 years old) admitted for laboratory-confirmed influenza and/or RSV infection in three tertiary hospitals in Portugal, Italy, and Cyprus over two consecutive winter seasons. The outcomes included the following: pneumonia on infection presentation, use of non-invasive ventilation (NIV), and in-hospital death (IHD). The association with possible predictors, including clinical features and type of virus infection, was assessed using uni- and multivariable analyses. A total of 251 oldest-old patients were included in the study. Pneumonia was evident in 32.3% (n = 81). NIV was implemented in 8.8% (n = 22), and IHD occurred in 13.9% (n = 35). Multivariable analyses revealed that chronic obstructive pulmonary disease (COPD) or asthma was associated with pneumonia (OR 1.86; 95% CI 1.02-3.43; p = 0.045). COPD or asthma (OR 4.4; 95% CI 1.67-11.6; p = 0.003), RSV (OR 3.12; 95% CI 1.09-8.92; p = 0.023), and influenza B infections (OR 3.77; 95% CI 1.06-13.5; p = 0.041) were associated with NIV use, respectively, while chronic kidney disease was associated with IHD (OR 2.50; 95% CI 1.14-5.51; p = 0.023). Among the oldest-old, chronic organ failure, such as COPD or asthma, and CKD predicted pneumonia and IHD, respectively, beyond the importance of viral virulence itself. These findings could impact on public health policies, such as fostering influenza immunization campaigns, home-based care programs, and end-of-life care. Filling knowledge gaps is crucial to set priorities and advise on transition model of care that best fits the oldest-old.