Relationship of Vascular Endothelial Growth Factor C, a Lymphangiogenesis Modulator, With Edema Formation, Congestion and Outcomes in Acute Heart Failure.

BACKGROUND: Although vascular endothelial growth factor C (VEGF-C) is a known lymphangiogenesis modulator, its relationship with congestion formation and outcomes in acute heart failure (AHF) is unknown. METHODS: Serum VEGF-C levels were measured in 237 patients hospitalized for AHF. The population was stratified by VEGF-C levels and linked with clinical signs of congestion and outcomes. RESULTS: The study's population was divided in VEGF-C tertiles: low (median [Q25-Q75]: 33 [15-175]), medium (606 [468-741]) and high (1141 [968-1442] pg/mL). The group with low VEGF-C on admission presented with the highest prevalence of severe lower-extremity edema (low VEGF-C vs medium VEGF-C vs high VEGF-C): 30% vs 13% vs 20%; P = 0.02); the highest percentage of patients with ascites: 22% vs 9% vs 6%; P = 0.006; and the lowest proportion of patients with pulmonary congestion: 22% vs 30% vs 46%; P = 0.004. The 1-year mortality rate was the highest in the low VEGF-C tertile: 35% vs 28% vs 18%, respectively; P = 0.049. The same pattern was observed for the composite endpoint (death and AHF rehospitalization): 45% vs 43% vs 26%; P = 0.029. The risks of death at 1-year follow-up and composite endpoint were significantly lower in the high VEGF-C group. CONCLUSIONS: Low VEGF-C was associated with more severe signs of congestion (signs of fluid accumulation) and adverse clinical outcomes.

Safety, feasibility, and effectiveness of a CT-guided transthoracic lung and pleural biopsy - a single-centre experience with own low-dose protocol.

Purpose: To assess the efficacy and safety of a low-dose, computed tomography (CT)-guided transthoracic biopsy of lung and pleural lesions. Material and methods: A total of 135 low-dose, CT-guided transthoracic lung and pleural lesions biopsies were performed. A cutting needle was utilized in 124 cases, and fine needle aspiration biopsy was performed in 14 cases. In all cases, 14- to 22-gauge biopsy needles were used. Results: Diagnostic material was obtained in 111 (82.2%) patients. In 97 (71.8%) cases neoplastic lesions were found, predominantly adenocarcinoma and non-small cell carcinoma. In 14 (12.6%) cases non atypical cells were reported. Biopsy failed to obtain material suitable for histopathological examination in 24 (17.7%) cases. Complications occurred in 31 patients, including pneumothorax in 28 patients and haematoma in 3 cases. Conclusions: Based on the obtained results, it can be stated that low-dose, CT-guided transthoracic biopsy of lung and pleural tissues is an accurate and safe procedure. Also, it is linked to a low risk of complications such as a small pneumothorax.

Image Quality Improvement in Deep Learning Image Reconstruction of Head Computed Tomography Examination.

In this study, we assess image quality in computed tomography scans reconstructed via DLIR (Deep Learning Image Reconstruction) and compare it with iterative reconstruction ASIR-V (Adaptive Statistical Iterative Reconstruction) in CT (computed tomography) scans of the head. The CT scans of 109 patients were subjected to both objective and subjective evaluation of image quality. The objective evaluation was based on the SNR (signal-to-noise ratio) and CNR (contrast-to-noise ratio) of the brain's gray and white matter. The regions of interest for our study were set in the BGA (basal ganglia area) and PCF (posterior cranial fossa). Simultaneously, a subjective assessment of image quality, based on brain structure visibility, was conducted by experienced radiologists. In the assessed scans, we obtained up to a 54% increase in SNR for gray matter and a 60% increase for white matter using DLIR in comparison to ASIR-V. Moreover, we achieved a CNR increment of 58% in the BGA structures and 50% in the PCF. In the subjective assessment of the obtained images, DLIR had a mean rating score of 2.8, compared to the mean score of 2.6 for ASIR-V images. In conclusion, DLIR shows improved image quality compared to the standard iterative reconstruction of CT images of the head.

Dynamic CT Myocardial Perfusion: The Role of Functional Evaluation in the Diagnosis of Coronary Artery Disease.

Coronary computed tomography angiography (CTA) is a widely accepted, non-invasive diagnostic modality for the evaluation of patients with suspected coronary artery disease (CAD). However, a limitation of CTA is its inability to provide information on the hemodynamic significance of the coronary lesion. The recently developed stress dynamic CT perfusion technique has emerged as a potential solution to this diagnostic challenge. Dynamic CT myocardial perfusion provides information on the hemodynamic consequences of coronary stenosis and is used to detect myocardial ischemia. The combination of stress dynamic CT myocardial perfusion with CTA provides a comprehensive assessment that integrates anatomical and functional information. CT myocardial perfusion has been validated in several clinical studies and has shown comparable accuracy to Positron Emission Tomography (PET) and stress magnetic resonance imaging (MRI) in the diagnosis of hemodynamically significant coronary stenosis and superior performance to Single Photon Emission Computed Tomography (SPECT). More importantly, CTP-derived myocardial perfusion has been shown to have a strong correlation with FFR, and the use of CTP results in a reduction of negative catheterizations. In the context of suspected stable coronary artery disease, the CT protocol with dynamic perfusion imaging combined with CTA eliminates the need for additional testing, making it a convenient "one-stop-shop" method and an effective gatekeeper to an invasive approach.

Biomarkers of Myocardial Injury and Remodeling in Heart Failure.

With its complicated pathophysiology, high incidence and prevalence, heart failure remains a major public concern. In hopes of improving diagnosis, treatment and prognosis, the utility of many different biomarkers is researched vigorously around the world. In this review, biomarkers of myocardial remodeling and fibrosis (galectin-3, soluble isoform of suppression of tumorigenicity 2, matrix metalloproteinases, osteopontin, interleukin-6, syndecan-4, myostatin, procollagen type I C-terminal propeptide, procollagen type III N-terminal propeptide, vascular endothelial growth factor, nitric oxidase synthetase and asymmetric dimethylarginine), myocyte injury (heart-type fatty acid-binding protein, glutathione S-transferase P1 and heat shock protein 60), as well as iron metabolism (ferritin, transferrin saturation, soluble transferrin receptor and hepcidin), are considered in terms of possible clinical applicability and significance. Our short review consists of a summary of the aforementioned cardiovascular biomarkers' clinical relevance and perspectives.

Novel Biomarkers of Renal Dysfunction and Congestion in Heart Failure.

Heart failure is a major public health problem and, despite the constantly emerging, new, effective treatments, it remains a leading cause of morbidity and mortality. Reliable tools for early diagnosis and risk stratification are crucial in the management of HF. This explains a growing interest in the development of new biomarkers related to various pathophysiological mechanisms of HF. In the course of this review, we focused on the markers of congestion and renal dysfunction in terms of their interference with cardiovascular homeostasis. Congestion is a hallmark feature of heart failure, contributing to symptoms, morbidity, and hospitalizations of patients with HF and has, therefore, become a therapeutic target in AHF. On the other hand, impaired renal function by altering the volume status contributes to the development and progression of HF and serves as a marker of an adverse clinical outcome. Early detection of congestion and an adequate assessment of renal status are essential for the prompt administration of patient-tailored therapy. This review provides an insight into recent advances in the field of HF biomarkers that could be potentially implemented in diagnosis and risk stratification of patients with HF.

Serum Osmolarity and Vasopressin Concentration in Acute Heart Failure-Influence on Clinical Course and Outcome.

Neurohormone activation plays an important role in Acute Heart Failure (AHF) pathophysiology. Serum osmolarity can affect this activation causing vasopressin excretion. The role of serum osmolarity and vasopressin concentration and its interaction remain still unexplored in AHF. The objective of our study was to evaluate the relationship of serum osmolarity with clinical parameters, vasopressin concentration, in-hospital course, and outcomes in AHF patients. The study group consisted of 338 AHF patients (male (76.3%), mean age of 68 ± 13 years) with serum osmolarity calculated by the equation: 1.86 × sodium [mmol/L] + (glucose [mg/dL]/18) + (urea [mg/dL]/2.8) + 9 and divided into osmolarity quartiles marked as: low: <287 mOsm/L, intermediate low: 287−294 mOsm/L, intermediate high: 295−304 mOsm/L, and high: >304 mOsm/L. There was an increasing age gradient in the groups and patients differed in the occurrence of comorbidities and baseline clinical and laboratory parameters. Importantly, analysis revealed that vasopressin presented a linear correlation with osmolarity (r = −0.221, p = 0.003) and its concentration decreased with quartiles (61.6 [44.0−81.0] vs. 57.8 [50.0−77.3] vs. 52.7 [43.1−69.2] vs. 45.0 [30.7−60.7] pg/mL, respectively, p = 0.034). This association across quartiles was observed among de novo AHF (63.6 [55.3−94.5] vs. 58.0 [50.7−78.6] vs. 52.0 [46.0−58.0] vs. 38.0 [27.0−57.0] pg/mL, respectively, p = 0.022) and was not statistically significant in patients with acute decompensated heart failure (ADHF) (59.5 [37.4−80.0] vs. 52.0 [38.0−74.5] vs. 57.0 [38.0−79.0] vs. 50.0 [33.0−84.0] pg/mL, respectively, p = 0.849). The worsening of renal function episodes were more frequent in quartiles with higher osmolarity (4 vs. 2 vs. 13 vs. 11%, respectively, p = 0.018) and patients that belonged to the quartiles with low and high osmolarity were characterized more often by incidence of worsening heart failure (20 vs. 9 vs. 10 vs. 22%, respectively, p = 0.032). There was also a U-shape distribution in relation to one-year mortality (31 vs. 19 vs. 23 vs. 37%, respectively, p = 0.022). In conclusion, there was an association of serum osmolarity with clinical status and both in-hospital and out-of-hospital outcomes. Moreover, the linear dependence between vasopressin concentration and serum osmolarity in the AHF population was identified and was driven mainly by patients with de novo AHF which suggests different pathophysiological paths in ADHF and AHF de novo.

Clinical determinants and prognostic significance of hypocapnia in acute heart failure.

The aim of this research was to examine the prevalence of hyperventilation (defined by pCO2 value) among acute heart failure (AHF) patients and to link it with potential triggers and prognosis. All patients underwent dyspnea severity assessment and capillary blood examination on hospital admission and during hospitalization. Out of 241 AHF patients, 57(24%) were assigned to low pCO2 group (pCO2 ≤ 30 mmHg) and 184 (76%) to normal pCO2 group (pCO2 > 30 mmHg). Low pCO2 group had significantly lower HCO3- (22.3 ± 3.4 vs 24.7 ± 2.9 mmol/L, p < 0.0001) and significantly higher lactate level (2.53 ± 1.6 vs 2.14 ± 0.97 mmol/L, p = 0.03). No differences between groups were observed in respect to the following potential triggers of hyperventilation: hypoxia (sO2 92.5 ± 5.2 vs 92 ± 5.6% p = 0.57), infection (CRP 10.5[4.9-26.4]vs 7.15[3.45-17.35] mg/L, p = 0.47), dyspnea severity (7.8 ± 2.3vs 8.0 ± 2.3 points, p = 0.59) and pulmonary congestion (82.5 vs 89.1%, p = 0.19), respectively. Low pCO2 value was related to an increased 4-year all-cause mortality hazard ratio (HR) (95% CI) 2.2 (1.3-3.6); p = 0.002 and risk of death and of rehospitalization for HF, HR (95% CI) 2.0 (1.3-3.0); p = 0.002. Hyperventilation is relatively frequent in AHF and is related to poor prognosis. Low pCO2 was not contingent on expected potential triggers of dyspnea but rather on tissue hypoperfusion.

Novel Phenotyping for Acute Heart Failure-Unsupervised Machine Learning-Based Approach.

Acute heart failure (AHF) is a life-threatening, heterogeneous disease requiring urgent diagnosis and treatment. The clinical severity and medical procedures differ according to a complex interplay between the deterioration cause, underlying cardiac substrate, and comorbidities. This study aimed to analyze the natural phenotypic heterogeneity of the AHF population and evaluate the possibilities offered by clustering (unsupervised machine-learning technique) in a medical data assessment. We evaluated data from 381 AHF patients. Sixty-three clinical and biochemical features were assessed at the admission of the patients and were included in the analysis after the preprocessing. The K-medoids algorithm was implemented to create the clusters, and optimization, based on the Davies-Bouldin index, was used. The clustering was performed while blinded to the outcome. The outcome associations were evaluated using the Kaplan-Meier curves and Cox proportional-hazards regressions. The algorithm distinguished six clusters that differed significantly in 58 variables concerning i.e., etiology, clinical status, comorbidities, laboratory parameters and lifestyle factors. The clusters differed in terms of the one-year mortality (p = 0.002). Using the clustering techniques, we extracted six phenotypes from AHF patients with distinct clinical characteristics and outcomes. Our results can be valuable for future trial constructions and customized treatment.

Renal profiling based on estimated glomerular filtration rate and spot urine sodium identifies high-risk acute heart failure patients.

AIMS: In acute heart failure (AHF), assessment of renal function comprises estimation of glomerular filtration rate (eGFR), which does not provide any information about renal sodium/water handling. We describe the interactions between urinary sodium concentration and eGFR to better characterize AHF patients. METHODS AND RESULTS: In 219 patients with AHF, spot urine sodium (UNa+ ) and eGFR were assessed on admission, day 1 and day 2 of hospitalization. We found no correlation between UNa+ and eGFR (calculated on each consecutive day, as an average of all three values, and as changes from baseline; all P > 0.05). The population was subsequently divided into four profiles based on eGFR (preserved vs. impaired; cutoff of 60 mL/min/1.73 m2 ) and UNa+ (sodium excreter vs. non-excreter; cutoff of 60 mmol/L). At day 1, there were 70 (31.9%) patients classified as preserved eGFR/sodium excreter, 37 (16.8%) as impaired eGFR/sodium non-excreter, 72 (32.9%) as impaired eGFR/sodium excreter, and 40 (18%) as preserved eGFR/sodium non-excreter. Both sodium non-excreter profiles were associated with an increased risk of in-hospital heart failure worsening [odds ratio (OR) 2.8, 95% confidence interval (CI) 1.3-6.4], inotrope use (OR 2.6, 95% CI 1.1-6.7) and rehospitalization due to AHF (OR 3.2, 95% CI 1.6-6.2; all P < 0.05). The preserved eGFR/sodium non-excreter profile was associated with highest 1-year mortality (52.5%) and remained an independent prognosticator after adjustment for other prognosticators (hazard ratio 2.9, 95% CI 1.7-5.2; P < 0.0005). CONCLUSIONS: In AHF, values of spot UNa+ and eGFR are not interrelated. Concomitant assessment of eGFR and spot UNa+ may be useful for better clinical and therapeutic profiling of patients.