The Impact of Cardiovascular and Lung Comorbidities in Patients with Pulmonary Arterial Hypertension: A Systematic Review and Meta-analysis.

BACKGROUND: Contemporary patients with pulmonary arterial hypertension (PAH) are older and exhibit cardiovascular and/or lung comorbidities. Such patients have typically been excluded from major PAH drug trials. This systematic review compares baseline characteristics, hemodynamic parameters, and mortality rate between PAH patients with significant number of comorbidities compared to those with fewer or no comorbidities. ΜETHODS: A systematic literature search in PubMed and Cochrane databases was conducted searching for studies comparing PAH patients with more than two cardiovascular comorbidities and/or at least a lung comorbidity against those with fewer comorbidities. RESULTS: Seven observational studies were included. PAH patients with comorbidities were older, with an almost equal female-to-male ratio, shorter 6-minute walk distance, higher NT-proBNP levels, and lower lung diffusion for carbon monoxide. In terms of hemodynamics, they had higher mean right atrial pressure and pulmonary artery wedge pressure, lower mean pulmonary arterial pressure, pulmonary vascular resistance and mixed venous oxygen saturation. Pooled analysis of six studies demonstrated a higher mortality risk for PAH patients with comorbidities compared to those without (HR 1.86, 95% CI 1.20 to 2.89, p<0.001, I²=92%), with the subgroup of PAH patients with lung comorbidities having an even higher mortality risk (test for subgroup differences: p<0.001). Combination drug therapy for PAH was less frequently used in patients with comorbidities. CONCLUSIONS: Cardiovascular and lung comorbidities impact the clinical characteristics and outcomes of PAH patients, highlighting the need for optimal phenotyping and tailored management for this high-risk population.

Unveiling the Role of Endothelial Dysfunction: A Possible Key to Enhancing Catheter Ablation Success in Atrial Fibrillation.

Atrial fibrillation, a prevalent type of arrhythmia, is increasingly contributing to the economic burden on healthcare systems. The development of innovative treatments, notably catheter ablation, has demonstrated both impressive and promising outcomes. However, these treatments have not yet fully replaced pharmaceutical approaches, primarily due to the relatively high incidence of atrial fibrillation recurrence post-procedure. Recent insights into endothelial dysfunction have shed light on its role in both the onset and progression of atrial fibrillation. This emerging understanding suggests that endothelial function might significantly influence the effectiveness of catheter ablation. Consequently, a deeper exploration into endothelial dynamics could potentially elevate the status of catheter ablation, positioning it as a primary treatment option for atrial fibrillation.

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.

Novel Approaches to the Management of Diabetes Mellitus in Patients with Coronary Artery Disease.

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in individuals with diabetes mellitus (DM). Although benefit has been attributed to the strict control of hyperglycemia with traditional antidiabetic treatments, novel antidiabetic medications have demonstrated cardiovascular (CV) safety and benefits by reducing major adverse cardiac events, improving heart failure (HF), and decreasing CVD-related mortality. Emerging data underline the interrelation between diabetes, as a metabolic disorder, and inflammation, endothelial dysfunction, and oxidative stress in the pathogenesis of microvascular and macrovascular complications. Conventional glucose-lowering medications demonstrate controversial CV effects. Dipeptidyl peptidase- 4 inhibitors have not only failed to prove to be beneficial in patients with coronary artery disease, but also their safety is questionable for the treatment of patients with CVD. However, metformin, as the first-line option for type 2 DM (T2DM), shows CVD protective properties for DM-induced atherosclerotic and macrovascular complications. Thiazolidinedione and sulfonylureas have questionable effects, as evidence from large studies shows a reduction in the risk of CV events and deaths, but with an increased rate of hospitalization for HF. Moreover, several studies have revealed that insulin monotherapy for T2DM treatment increases the risk of major CV events and deaths from HF, when compared to metformin, although it may reduce the risk of myocardial infarction. Finally, this review aimed to summarize the mechanisms of action of novel antidiabetic drugs acting as glucagon-like peptide-1 receptor agonists and sodium-glucose co-transporter-2 inhibitors that show favorable effects on blood pressure, lipid levels, and inflammation, leading to reduced CVD risk in T2DM patients.

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.

Adherence to inhalers and comorbidities in COPD patients. A cross-sectional primary care study from Greece.

BACKGROUND: Comorbidities and adherence to inhaled therapy appears to have a major impact on treatment goals, health status and disease control in chronic obstructive pulmonary disease (COPD). Aim of the study was to assess levels of adherence to inhalers, comorbidities and associations with COPD outcomes in patients residing in rural and semi-urban areas of Greece. METHODS: Two hundred fifty-seven COPD patients were enrolled from primary health care in 2015-2016. Physicians used structured interviews and questionnaires to assess quality of life and disease status. Patients were classified into groups according to GOLD 2019 guidelines (based on CAT and mMRC). Adherence to inhalers was measured with the Test of Adherence to Inhalers (TAI). Multivariate linear and logistics regression models were used to assess associations between comorbidities and adherence to inhalers with COPD outcomes, including CAT and mMRC scores, exacerbations and GOLD A-D status. RESULTS: 74.1% of COPD patients reported poor adherence, while most of them were characterized as deliberate non-compliers (69.5%). 77.1% had ≥2 comorbidities, with overweight/obese (82.2%), hypertension (72.9%) and diabetes mellitus (58%) being the most prevalent. In multivariate analysis, COPD outcomes having significant associations with poor adherence included worse health status [OR (95% CI) 4.86 (1.61-14.69) and 2.93 (1.51-5.71) based on CAT and mMRC, respectively], having ≥2 exacerbations in the past year [4.68 (1.51-4.44)], and disease status e.g., be in groups C or D [3.13 (1.49-8.53) and 3.35 (1.24-9.09) based on CAT and mMRC, respectively). Subjects with gastroesophageal reflux showed better inhaler adherence [OR (95% CI) 0.17 (0.6-0.45)], but none of the comorbid conditions was associated with COPD outcomes after adjustments. CONCLUSIONS: Poor adherence to inhalers and comorbidities are both prevalent in COPD patients of primary care residing in rural/semi-urban areas of Greece, with adherence influencing COPD outcomes. Raising awareness of patients and physicians on the importance of comorbidities control and inhaler adherence may lead to interventions and improve outcomes.

Associations of sense of coherence and self-efficacy with health status and disease severity in COPD.

Sense of coherence and self-efficacy has been found to affect health-related quality of life in chronic diseases. However, research on respiratory diseases is limited. Here we report findings on quality of life (QoL) of COPD patients and the associations with coherence and self-efficacy. This study consists of the Greek national branch of the UNLOCK study, with a sample of 257 COPD patients. Coherence and self-efficacy are positively inter-correlated (Pearson rho = 0.590, p < 0.001). They are negatively correlated with the quality of life (CAT) [Pearson rho: coherence = -0.29, p < 0.001; self-efficacy = -0.29, p < 0.001) and mMRC (coherence = -0.37, p < 0.001; self-efficacy rho = -0.32, p < 0.001)]. Coherence is inversely associated with (Global Initiative for Chronic Obstructive Lung Disease) GOLD 2018-CAT and GOLD 2018-mMRC classification and "having at least one exacerbation in the past year". Findings are stressing the need for their incorporation in primary health care and COPD guidance as it maybe that enhancing coherence and self-efficacy will improve QoL.

Validation of a Proposed Algorithm for Assistance Titration During Proportional Assist Ventilation With Load-Adjustable Gain Factors.

BACKGROUND: The present study aimed to validate a recently proposed algorithm for assistance titration during proportional assist ventilation with load-adjustable gain factors, based on a noninvasive estimation of maximum inspiratory pressure (peak Pmus) and inspiratory effort (pressure-time product [PTP] peak Pmus). METHODS: Retrospective analysis of the recordings obtained from 26 subjects ventilated on proportional assist ventilation with load-adjustable gain factors under different conditions, each considered as an experimental case. The estimated inspiratory output (peak Pmus) and effort (PTP-peak Pmus) were compared with the actual-determined by the measurement of transdiaphragmatic pressure- and the derived PTP. Validation of the algorithm was performed by assessing the accuracy of peak Pmus in predicting the actual inspiratory muscle effort and indicating the appropriate level of assist. RESULTS: In the 63 experimental cases analyzed, a limited agreement was observed between the estimated and the actual inspiratory muscle pressure (-11 to 10 cm H2O) and effort (-82 to 125 cm H2O × s/min). The sensitivity and specificity of peak Pmus to predict the range of the actual inspiratory effort was 81.2% and 58.1%, respectively. In 49% of experimental cases, the level of assist indicated by the algorithm differed from that indicated by the transdiaphragmatic pressure and PTP. CONCLUSIONS: The proposed algorithm had limited accuracy in estimating inspiratory muscle effort and with indicating the appropriate level of assist.

Determinants of frailty in primary care patients with COPD: the Greek UNLOCK study.

BACKGROUND: Frailty is a state of increased vulnerability that has a significant risk of unfavorable outcomes such as increased dependency and/or death, but little is known about frailty in people with chronic obstructive pulmonary disease (COPD). METHOD: We aimed to determine the prevalence of frailty in COPD patients and to identify the associated risk factors. Two hundred fifty-seven COPD patients enrolled from primary care in Greece between 2015 and 2016. Physicians used structured interviews to collect cross-sectional data including demographics, medical history, symptoms and COPD Assessment Tool (CAT) or modified Medical Research Council Dyspnea scale (mMRC) score. Patients were classified into severity groups according to GOLD 2017 guidelines. Participants completed the The Frail Non-Disabled (FiND) questionnaire, exploring the frailty and disability domains. In the present analyses, frail patients with and without mobility disability were pooled and were compared to non-frail patients. Factors associated with frailty were analyzed using univariate and multivariate logistic regression. RESULTS: Mean (SD) age was 65 (12.3) with 79% males. The majority of patients suffered with frailty (82%) of which 76.8% had mobility disability. 84.2% were married/with partner and 55.4% retired. 55.6% were current smokers. Uncontrolled disease (≥10 CAT score) was reported in 91.1% and 37.2% of patients had ≥2 exacerbations in the past year. Dyspnea (38%) and cough (53.4%) were the main symptoms. Main comorbidities were hypertension (72.9%), hyperlipidaemia (24.6%) and diabetes (11%). Risk of frailty was significantly increased with age (OR; 95%CI: 1.05; 1.02-1.08), hypertension (2.25; 1.14-4.45), uncontrolled disease (≥10 CAT score 4.65; 1.86-11.63, ≥2 mMRC score 5.75 (2.79-11.85) or ≥ 2 exacerbations 1.73; 1.07-2.78), smoking cessation (ex compared to current smokers: 2.37; 1.10-5.28) and GOLD status (B&D compared to A&C groups: CAT-based 4.65; 1.86-11.63; mMRC-based: 5.75; 2.79-11.85). In multivariate regression smoking cessation and GOLD status remained significant. Gender, body mass index, occupational or marital status, symptoms and other comorbidities were not significant. CONCLUSIONS: Frailty with mobility disability is common in COPD patients and severity of disease increases the risk. It is possible that frail patients are more likely to quit smoking perhaps because of their disability and uncontolled disease. Routine assessment of frailty in addition to COPD control may allow early interventions for preventing or delaying progression of frailty and improvement in COPD disease.

Non-typhoidal Salmonella myocarditis in an immunocompetent young adult with diarrhea.

Myocarditis is the inflammation of the heart muscle and it is caused by a wide range of infectious and non-infectious conditions. Non-typhoidal Salmonella infection, a common foodborne illness worldwide, only rarely causes myocarditis. We describe a case of an immunocompetent adult with Salmonella enterica serovar Typhimurium myocarditis who had a favorable outcome due to early recognition of the causative factor and prompt initiation of appropriate treatment.

Varicella-zoster virus meningitis with hypoglycorrhachia in a young immunocompetent adult without rash: A case report and literature review.

Overt aseptic meningitis rarely complicates varicella-zoster virus (VZV) reactivation in young and immunocompetent adults. Many of the cases of VZV meningitis are associated with an exanthem. We describe an otherwise healthy 36-year-old adult who had aseptic meningitis without skin rash, caused by reactivation of varicella-zoster virus. Cerebrospinal fluid (CSF) analysis revealed lymphocytosis, increased total protein, and low glucose. Diagnosis was made by polymerase chain reaction in CSF. The present case highlights the fact that VZV should be considered as a cause of aseptic meningitis with hypoglycorrhachia in healthy and young individuals, even in the absence of an exanthem.

Characteristics and predictors of outcome of spontaneous spinal epidural abscesses treated conservatively: A retrospective cohort study in a referral center.

OBJECTIVE: Recent studies have shown that in carefully selected patients, conservative treatment alone can be an option in the management of spinal epidural abscess (SEA). The aim of this study was to identify prognostic factors of outcome in patients with spontaneous SEA treated conservatively. PATIENTS AND METHODS: A retrospective cohort study of all patients with spontaneous SEA treated with antibiotics alone from January 2012 to December 2015 was conducted in a 1200-bed tertiary referral center. Demographic, clinical, microbiological, and radiological characteristics were analyzed. Failure of medical treatment was defined as the need for delayed surgical intervention, no neurological improvement or deterioration, death due to the infection, or relapse after hospital discharge. RESULTS: We identified 21 patients diagnosed with spontaneous SEA treated conservatively. Median age was 72 years and 10 patients were male. Eleven patients presented with radicular weakness and/or radicular sensory deficit, or incomplete cord injury. Inflammatory markers were markedly elevated in all patients. Thirteen patients were successfully treated with conservative treatment, while among 8 patients with treatment failure, 1 died due to the infection. Presence of serious neurological deficits and infection due to methicillin-resistant S. aureus (MRSA) were associated with failure of conservative treatment. Notably, neither the extension nor the location of the abscess on magnetic resonance imaging (MRI) was associated with failed medical management. CONCLUSIONS: A significant proportion of patients with spontaneous SEA can respond to antibiotic treatment alone. However, in patients with infection due to MRSA or with severe neurological impairment, conservative management has an increased risk of failure.