Median Level Research Articles

Assessment of hemodynamic parameters and caudal vena cava-to-aorta ratio pre- and post-pericardiocentesis in dogs with cardiac tamponade.

To evaluate haemodynamic parameters and ultrasonographic measurements of the caudal vena-cava-to-aorta ratio at the splenorenal view in canine cardiac tamponade before and 30 minutes after pericardiocentesis. Dogs presenting with cardiac tamponade at two veterinary hospitals were included. Triage examination, noninvasive systolic arterial blood pressure, shock index, venous lactatemia and POCUS results were recorded at admission and 30 minutes after pericardiocentesis. This prospective observational study included 22 dogs, and all had an increased caudal vena-cava-to-aorta ratio. After pericardiocentesis, there were significant changes in vital signs, including a decrease in the median heart rate by 42.1%, a decrease in the median respiratory rate by 40.1%, and an increase in the median rectal temperature from 37.8°C (range: 35.6 to 39.2) to 38.1°C ( 36.1 to 38.7). In regards of hemodynamic parameters, the median systolic arterial pressure increased significantly by 23.2%, the shock index decreased significantly by 52.8%, the median lactate level decreased significantly from 6.1 mmol/L (1.4 to 14.7) to 3.6 mmol/L (1.1 to 13.6), and the median caudal vena-cava-to-aorta ratio decreased significantly by 37.5%, from 1.76 (1.35 to 2.13) to 1.12 (0.91 to 1.51). This study demonstrated an increased caudal vena-cava-to-aorta ratio in dogs with cardiac tamponade and a rapid haemodynamic improvement in dogs with cardiac tamponade within 30 minutes of the pericardiocentesis, resulting in excellent short-term prognosis.

Nonalcoholic Fatty Liver Disease Risk and Proprotein Convertase Subtilisin Kexin 9 in Familial Hypercholesterolemia Under Statin Treatment.

Fatty acids are involved in some hepatic disorders. The proprotein convertase subtilisin kexin 9 (PCSK9) inhibits the uptake of low-density lipoproteins (LDLs), which contain lipids, into the liver and may thus be associated with nonalcoholic fatty liver disease (NAFLD), a cardiovascular disorder (CVD) risk. Statins reduce blood LDL-cholesterol (LDL-C) levels and CVD risk and can attenuate the development of NAFLD while increasing blood PCSK9 levels. We investigated the correlation between PCSK9 and liver conditions in patients with familial hypercholesterolemia (FH), a CVD risk population with elevated blood LDL-C levels, under statin treatment. Blood tests for lipids, PCSK9, and liver function (aspartate aminotransferase [AST] and alanine aminotransferase [ALT]) were performed in patients with FH taking statins (n = 25, mean age = 57 years, 12% of males). The ALT:AST ratio was used as a marker of NAFLD risk. The mean LDL-C level was 3.38 mmol/L, and the median PCSK9 level was 312 ng/mL. The median ALT:AST ratio was 0.88. A significant negative correlation was observed between the PCSK9 and ALT:AST ratio (β = -0.67, p < 0.05). Their negative correlation might give a hypothetical insight into the effect of statin treatment on the development of NAFLD, in relation to PCSK9 behavior, in patients with FH.

Circulating Angiopoietin-2 (Angpt2) levels predict diagnosis of Chronic Thromboembolic Pulmonary Hypertension (CTEPH)

Abstract Background Vascular remodeling following incomplete thrombus resolution is considered to be a key factor in the progression to chronic thromboembolic pulmonary hypertension (CTEPH) after acute pulmonary embolism (PE). Recent data demonstrated that Angpt2, which controls signaling via the Tie2 receptor, could interfere with the normal process of thrombus resolution. Our prior findings have shown that patients presenting with acute PE and having plasma levels of Angt-2 ≥5.5 ng/ml at admission are at a significantly increased risk (93 times higher) of being diagnosed with CTEPH in subsequent assessments. Purpose To externally validate the prognostic performance of Angpt2 for the development of CTEPH. Methods In a prospective cohort study of unselected consecutive all-comers with PE, survivors of the index acute event underwent 3-, 12- and 24-month follow-up with venous blood sampling for subsequent biomarker measurements. Angpt2 was measured on admission using specific enzyme linked immunosorbent assays (ELISA) detecting both the endogenous and the recombinant protein, according to the manufacturer (R&amp;D Systems). Results Overall, 319 patients with acute PE (median age: 62 [IQR, 50-73]; females: 55.2%) were included in the analysis with a median Angpt2 plasma level of 2.6 ng/ml (IQR, 1.8-3.7) (Figure 1). Patients with PE and Angpt-2 plasma levels above the median had more often comorbidities, such as chronic heart failure (24.2% and 11.0.%; p=0.045), chronic kidney disease (33.3% vs 14.0%; p=0.010), or diabetes (27.3% vs. 12.9%; p=0.032). Angpt2 plasma levels correlated with haemodynamic status and parameters indicating severe PE (right ventricle dysfunction, r=0.129 [p=0.021) and troponin, r=0.246 [p&amp;lt;0.001]). In total, post-PE impairment (PPEI) was diagnosed in 33 (10.3%) and CTEPH in four (1.3%) patients during follow-up. Angpt2 plasma levels were higher on admission in patients developing PPEI or CTEPH during follow-up compared to patients without PPEI or CTEPH (PPEI vs non-PPEI: median, 3.2 [2.3-4.1] ng/ml vs. 2.5 [1-3.4] ng/ml, p=0.035; CTEPH vs. non-CTEPH: median, 5.1 [2.9-10.5] ng/ml vs. 2.5 [1.7-3.6] ng/ml, p=0.055). Regarding the diagnosis of CTEPH during follow-up, ROC analysis illustrated an AUC for Angpt2 (0.779 [95% CI 0.56–0.99]; p=0.055]) (Figure 2). By using univariate logistic regression analysis, the calculated predefined Angpt2 cut-off value of ≥5.5 ng/ml was associated with a 9.2-fold increased risk (1.3–67.4, p=0.030) for a diagnosis of CTEPH during follow-up. Conclusion We were able to validate in a different patient cohort the usefulness of Angpt2 as a novel biomarker to identify patients at risk for CTEPH.

An ovine septic shock model of live bacterial infusion

BackgroundEscherichia coli is the most common cause of human bloodstream infections and bacterial sepsis/septic shock. However, translation of preclinical septic shock resuscitative therapies remains limited mainly due to low-fidelity of available models in mimicking clinical illness. To overcome the translational barrier, we sought to replicate sepsis complexity by creating an acutely critically-ill preclinical bacterial septic shock model undergoing active 48-h intensive care management.AimTo develop a clinically relevant large-animal (ovine) live-bacterial infusion model for septic shock.MethodsSeptic shock was induced by intravenous infusion of the live antibiotic resistant extra-intestinal pathogenic E. coli sequence type 131 strain EC958 in eight anesthetised and mechanically ventilated sheep. A bacterial dose range of 2 × 105–2 × 109 cfu/mL was used for the dose optimisation phase (n = 4) and upon dose confirmation the model was developed (n = 5). Post-shock the animals underwent an early-vasopressor and volume-restriction resuscitation strategy with active haemodynamic management and monitoring over 48 h. Serial blood samples were collected for testing of pro-inflammatory (IL-6, IL-8, VEGFA) and anti-inflammatory (IL-10) cytokines and hyaluronan assay to assess endothelial integrity. Tissue samples were collected for histopathology and transmission electron microscopy.ResultsThe 2 × 107 cfu/mL bacterial dose led to a reproducible distributive shock within a pre-determined 12-h period. Five sheep were used to demonstrate consistency of the model. Bacterial infusion led to development of septic shock in all animals. The baseline mean arterial blood pressure reduced from a median of 91 mmHg (71, 102) to 50 mmHg (48, 57) (p = 0.004) and lactate levels increased from a median of 0.5 mM (0.3, 0.8) to 2.1 mM (2.0, 2.3) (p = 0.02) post-shock. The baseline median hyaluronan levels increased significantly from 25 ng/mL (18, 86) to 168 ng/mL (86, 569), p = 0.05 but not the median vasopressor dependency index which increased within 1 h of resuscitation from zero to 0.39 mmHg−1 (0.06, 5.13), p = 0.065, and. Over the 48 h, there was a significant decrease in the systemic vascular resistance index (F = 7.46, p = 0.01) and increase in the pro-inflammatory cytokines [IL-6 (F = 8.90, p = 0.02), IL-8 (F = 5.28, p = 0.03), and VEGFA (F = 6.47, p = 0.02)].ConclusionsThis critically ill large-animal model was consistent in reproducing septic shock and will be applied in investigating advanced resuscitation and therapeutic interventions.

The gut-microbiome derived phenylacetylglutamine predicts adverse events in patients with acute coronary syndromes

Abstract Background and Introduction The gut microbiota-derived metabolite phenylacetylglutamine (PAG) is associated with incident cardiovascular events(1). Acute coronary syndromes (ACS) present a major health challenge, especially as population ages(2). Data from our group show increased PAG levels during aging in humans. However, the predictive potential of PAG for mortality and major adverse cardiovascular events (MACE) in patients (pts) with ACS is unknown. Purpose Here, we investigated the potential of PAG to predict ischemic and fatal events in pts with acute coronary syndromes (ACS). We also compared the predictive potential of PAG to another relevant gut-microbiota derived metabolite involved in CVD, namely Trimethylaminoxyde, (TMAO), and we evaluated their cumulative risk potential. Methods A total of 1’848 patients were enrolled in Cohort I of the SPUM-ACS study – a multi-center prospective ACS cohort study from Switzerland. Overall survival and incident MACE after 1 year follow-up were analyzed using Kaplan-Meier (KM) estimates and compared by log-rank test after patient stratification into PAG tertiles. Uni- and multivariable Cox-regression models were fit to calculate the hazard ratios for 1-year MACE in a crude model and adjusted model (adjusted for established confounders). Healthy controls served as additional controls. PAG plasma levels were quantified using LC-HRMS. Results The median PAG plasma level in the healthy control group was 1.76µM, whereas for the whole ACS patient population it was 1.92µM (Table 1). Pts in the third PAG tertile had a two times higher MACE rate and a four times higher mortality rate compared to pts in the first PAG tertile (p&amp;lt;0.001). (Table 2). PAG levels were significantly higher in pts who presented with MACE (2.63µM) or died (3.1µM) within the 1-year follow-up compared to the healthy control subjects (p&amp;lt;0.0001) (Figure 1A). Spearman correlation analysis revealed that plasma PAG levels were positively associated with age (r=0.43, p&amp;lt;0.0001), while a negative association with eGFR was observed (r=-0.51, p&amp;lt;0.0001) (Figure 1B). KM estimates indicated that pts in the highest PAG tertile had significantly higher 1-year MACE risk relative to those with low levels (Figure 1C; p&amp;lt;0.001 log rank). Following multivariable adjustment, PAG remained an independent predictor for MACE at 1-year follow-up with a hazard ratio (HR) of 1.8 (95% CI, 1.1–3.2, p=0.048) (Figure 1D). KM estimates of both, high levels of PAG and high levels of TMAO together, indicate that the combination of these two detrimental metabolites leads to an even higher risk of 1-year MACE relative to lower levels (Figure 1E). Conclusion PAG is a novel and independent predictor of adverse outcomes in patients with ACS. This study indicates the role of the gut-microbiome and its metabolites in predicting ischemic and fatal outcomes of pts with established CVD.

Prognostic value of IL-22 levels and the TH17 pathway in patients with acute myocardial infarction

Abstract Introduction Acute myocardial infarction (AMI) induces a surge in inflammatory cytokines and cells including T helper cells (TH). TH17 cells are activated by pro-inflammatory cytokines such as IL-1, IL-6, and IL-21; they secrete IL-17 and IL-22 to promote neutrophil chemotaxis and to induce pro-inflammatory cytokine secretion from macrophages. Purpose We aimed to explore the prognostic value of the TH17 pathway and its component cytokines in AMI patients. Methods Patients with AMI (STEMI and NSTEMI) were included from the SPUM-ACS cohort (total N=4,787) selecting a time window &amp;lt;24 h from symptom onset to blood sampling before PCI. Patients with malignancies or immunosuppressive therapies were excluded. 160 patients who experienced death (N=85) or recurrent AMI (N=75) within 1-year follow-up (AMI-case) were compared to 152 counterparts with favorable outcome matched for age, sex, AMI subtype, and onset time (AMI-control). 45 healthy blood donors (HD) without cardiovascular disease were added as a reference group. Cytokine levels were reported as median + IQR and were analyzed with multivariate linear regression. Group comparisons were made using the Mann-Whitney U test or Kruskal-Wallis test and multiple comparisons corrected with Dunn’s test. Kaplan-Meier curves were cut off at a median IL-22 level and tested with Log-rank test. Results Our measurement showed correlation among components in TH17 pathway. IL-22 was significantly associated with IL-1β (β=-3.027e-1, p=0.0164), IL-6 (β=5.413e-3, p&amp;lt;0.0001), and IL-21 (β=3.567e-2, p&amp;lt;0.0001), but not with IL-1α or IL-1RA. IL-22 was not correlated with IL-17. Age (median=71.45 vs 71.30 years, p&amp;gt;0.05), percentage of women (23.8% vs 19.7%, p&amp;gt;0.05), and percentage of STEMI (70.6% vs 69.7%, p&amp;gt;0.05) did not differ between AMI-case and AMI-control. AMI-case and AMI-control both showed higher plasma IL-22 levels than HD, whereas there was no difference between AMI groups (Figure 1A). AMI patients who died within 1-year follow-up had higher IL-22 levels than those with recurrent AMI (Figure 1B). Regarding TH17 activation, patients who died had higher IL-17 levels (Figure 1C). Median IL-22 (4.86 pg/mL) levels were tested for predicting outcome: Patients with higher IL-22 levels had more risk for death or recurrent AMI (p=0.0253, Figure 2A). The mortality of patients above median IL-22 levels was higher than those below (p=0.0126); The KM-curves diverged early in less than 1 month after the initial event (Figure 2B). Conclusions Upstream regulators (IL-1β, IL-6) correlated with downstream effectors (IL-22, IL-17) within the pathways involving TH17 cells. Both IL-22 and Il-17 were higher in AMI patients who died within one year than in similar patients who survived. Investigating TH-17- and IL-22-related pathways may be of interest for further investigation in patients with AMI.

The association of NT-proBNP levels in atrial fibrillation patients and 3-year risk of heart hospitalization and death

Abstract Background NT-proBNP-levels are often elevated in patients with atrial fibrillation (AF), but their clinical use and interpretation for predicting subsequent cardiovascular events has not been explored in an all-comers setting. Aim To determine whether NT-proBNP levels are associated with the risk of subsequent heart failure (CHF) and/or death in patients with AF and its relation to prior CHF diagnosis Method All patients with new-onset AF (defined by ICD-code I48) who had an NT-proBNP-level within +/- 14 days of the date of the AF date measured in a regional laboratory repository between 2000-2021 were included in the analysis cohort. Patients were categorized into NT-proBNP level (pg/mL) &amp;lt;1000, 1000-1999, ≥2000. If several NT-proBNP-levels were measured, the maximal value was used. The association between NT-proBNP level and the outcome CHF hospitalization and/or death within 3 years of diagnosis was assessed in Cox regression analyses adjusted for baseline characteristic and medications. Since there was an interaction (p&amp;lt;0.001) between Nt-proBNP-level and prior/new-onset CHF at time of AF diagnosis and no known CHF, two separate analyses were performed in patients with or new-onset CHF and those without prior CHF. Results There were 10559 patients with AF and no CHF, and 11 257 with AF and CHF. There were 14% of patients with new-onset CHF at time of new-onset AF diagnosis. These were grouped together with patients with known CHF. Patients with no prior CHF were younger (76 years (95% CI 68-83) vs 80 (72-87), p&amp;lt;0.001), and healthier with less often diabetes (18.4% vs 24.5%, p&amp;lt;0.001), prior myocardial infarction (12.0% vs 24.3%), a lower CHA2DS2-VASc score (3.0 vs 5.0, p&amp;lt;0.001) and a lower median NT-proBNP level (1650 pg/mL (95% CI 702-3549) vs 4240 pg/mL (2160-8860), p&amp;lt;0.001). Among patients with AF and no prior CHF, the incidence rate in the lowest NT-proBNP level was low, but increased with higher levels (Table). Adjusting for covariates and medications, the risk of both CHF hospitalization and CHF/death compared to the reference category NTproBNP&amp;lt; 1000 pg/mL was nearly 2 and 3 times higher among those who with initial NT-proBNP level 1000-1999 and ≥ 2000. Among patients with AF and known CHF, the incidence rate of CHF hospitalization or CHF hospitalization/death at the same NT-proBNP-strata was several times higher compared to patients without known CHF. Adjusting for covariates, the risk increased for CHF hospitalization or CHF/hospitalization similarly for each strata as for patients without known CHF. AF patients without known HF but with the highest elevation of NTproBNP-level had a risk of subsequent hospitalization of heart failure which was higher than those with known heart failure and lowest NTproBNP-level. Conclusion A higher NTproBNP-level in patients with AF identifies patients at higher risk of CHF hospitalization and/or death in both patients with no and prior CHF.Table

Smoking cessation after acute myocardial infarction: a Swiss-wide cohort study

Abstract Background Smoking is a major cardiovascular risk factor and of great importance in terms of both primary and secondary prevention. The present study aims to identify patient characteristics associated with smoking cessation within 1 year after acute myocardial infarction (AMI) to inform physician-patient interactions, secondary prevention measures, and public health planning. Methods ST-elevation myocardial infarction (STEMI) and non-STEMI (NSTEMI) patients enrolled between 2012 and 2022 in the AMIS Plus registry who were active smokers at the time of the index event were included. At the 1-year follow-up, patients were questioned about their smoking behaviour via telephone interview and were further classified into those who had quit (stoppers) or continued (continuers) smoking. Patient characteristics were collected at the time of the index event and at follow-up and then compared using descriptive statistics. Results From a total of 4523 patients with AMI, 4242 (93.8%) provided information regarding their smoking status at a median follow-up of 395 days (interquartile range 370 to 469) after the index event. Of 1691 (39.9%) active smokers at the time of AMI, 861 (50.9%) reported quitting whereas 830 (49.1%) were still smoking at the 1-year follow-up. Stoppers were younger (57 vs. 58 years, p&amp;lt;0.001), more likely to be male (82.8% vs. 77.7%, p=0.008) and have presented with STEMI (77.0% vs. 71.0%, p=0.005), and less likely to have had a previous AMI (6.6% vs. 13.3%, p&amp;lt;0.001) than continuers. Smoking cessation was more common in patients with a more severe AMI characterised by a greater extent of myocardial injury (in-hospital median peak creatine kinase level 1291 IU/L vs. 1101 IU/L, p=0.012), at least one in-hospital complication (13.9% vs. 9.9%, p=0.01), and participation in a rehabilitation programme (83.7% vs. 68.8%, p&amp;lt;0.001). Stoppers more frequently implemented other favourable lifestyle changes, such as dietary changes (56.2% vs. 45.2%, p&amp;lt;0.001) and increased physical activity (54.6% vs. 37.7%, p&amp;lt;0.001) than continuers. Self-reported weight gain was more prevalent among those who quit smoking (44.0% vs. 19.7%, p&amp;lt;0.001). Conclusions In Switzerland, half of the patients with AMI who were active smokers at the time of AMI, reported to have stopped smoking 1 year after the index event. Smoking cessation was associated with participation in a rehabilitation programme and occurred more often in patients with larger AMI sizes, higher in-hospital complication rates and more frequent implementation of other favourable lifestyle changes after AMI. The significant weight gain after smoking cessation seems to represent a major issue that should specifically be addressed.

Residual congestion in acute decompensated heart failure: A novel approach through microvascular imaging of renal circulation

Abstract Background In patients admitted for acute decompensated heart failure (ADHF), residual congestion at discharge is associated with adverse clinical outcomes. Traditionally, the extent of congestion has been inferred from central venous pressure, but it has also been highlighted that this is insufficient for a comprehensive evaluation of residual congestion. On the other hand, renal congestion is an important finding of organ congestion, and Superb Microvascular Imaging (SMI), a technique that reveals minute flow details, is promising for assessing renal circulation. We hypothesized that in patients with ADHF, assessment of renal circulation using SMI may be superior to conventional methods in assessing residual congestion. Methods In this prospective study, we enrolled 45 consecutive patients admitted with ADHF. We performed comprehensive evaluations including blood tests, echocardiography, and renal ultrasonography using SMI. The vascular index (VI), as measured by SMI, was calculated as the percentage of blood flow signal area in the region of interest. Subsequently, we calculated the intra-renal perfusion index (IRPI), representing cyclic variation in VI, as (maximum VI - minimum VI) within one cardiac cycle, divided by the maximum VI (Figure). Brain Natriuretic Peptide (BNP) levels were utilized to evaluate the state of decongestion. Results At discharge, the mean IRPI was 0.61±0.04, while the median BNP levels were 204.9 pg/ml (interquartile range: 102.7, 428.2). Patients exhibiting elevated log BNP levels at discharge (&amp;gt;2.31, based on median value) displayed significantly higher IRPI values [0.61(0.49, 0.86) vs 0.53(0.35, 0.59), p=0.02] and were older (80.8±8.5 vs 70.3±14.9 years, p=0.010). However, no significant differences were observed regarding laboratory parameters including hematocrit and creatinine levels, as well as echocardiographic parameters such as ejection fraction, E/e' ratio, and estimated right atrial pressure (RAP). Moreover, at discharge, creatinine levels (p=0.56) and estimated RAP (p=0.06) exhibited no significant correlation with IRPI. Conclusion Renal circulation evaluated by SMI may serve as a useful indicator of the extent of residual congestion at discharge compared to blood tests and echocardiographic estimates of right atrial pressure in patients admitted for ADHF.

Exercise oscillatory ventilation as a predictor of mortality in patients with amyloid cardiomyopathy

Abstract Background Exercise oscillatory ventilation (EOV) signals multiple abnormalities in hemodynamics and ventilatory control which may predict poor outcome in patients with cardiac diseases. Purpose To assess whether EOV (+) patients with amyloid cardiomyopathy show higher mortality rates compared to their counterparts without EOV. Methods We analyzed cardiopulmonary exercise testing results for EOV defined by continuous (&amp;gt;60% of exercise duration) oscillations in minute ventilation (VE), cycling with a frequency of one minute and an amplitude above 15% of resting VE, in patients with amyloid cardiomyopathy. Results 156 patients with amyloid cardiomyopathy, aged 78 (±7) years, 87% male with a NYHA functional class of II (49.4%) and median B-type natriuretic peptide levels of 2548 (1374-4703) ng/L. Comorbidities include hypertension (73.1%), polyneuropathy (45.5%), coronary heart disease (41.0%), diabetes mellitus (17.3%) and chronic obstructive pulmonary disease (10.9%). Patients had a mean peak oxygen consumption of 14.8 (±4.42) ml/kg·min and a VE to carbon dioxide production (VCO2) slope ≥ 40 in 67.9% of cases. EOV was seen in 38 (24.4%), clearly absent in 92 (59.0%) and not clearly differentiable in 26 (16.7%) patients. 33 (21.2%) had a HF-related hospitalization and 31 (19.9%) died. EOV shows a hazard ratio of 2.35 (CI 1.088 – 5.075, p-value &amp;lt;0.05) for all-cause mortality. In fact, the log-rank test showed a difference in survival time between patients with and without EOV (p=0.03) with a median survival time of 46 months. Conclusion EOV may improve the prognostic yield of incremental CPET in patients with amyloid cardiomyopathy.Kaplan-Meier Curve for EOV

Investigating the diverse role of ultra-processed foods on cardiometabolic multimorbidity: Highlights from the ATTICA prospective study (2002-2022)

Abstract Background/Introduction The role of ultra-processed foods (UPF) on multimorbidity is currently unknown with limited research implying the existence of complex associations among the diverse UPF categories. Purpose The aim of the present work was to investigate the association of total and subgroup intake of UPF with cardiometabolic multimorbidity, after twenty years of observation, in a Mediterranean region. Methods In 2001-2002, n=3,042 free-of-cardiovascular disease (CVD) men and women from Attica, Greece, were recruited. Dietary assessment was based on a validated semi-quantitative food frequency questionnaire. The NOVA Food Classification system was used to assign the food products as UPF using a standard methodology. The food products assigned as UPF were further grouped as "bread and cereals", "spreads and sauces", "sweets and desserts", "artificially and sugar-sweetened beverages", "processed meat products" and "savory snacks". Cardiometabolic multimorbidity was defined as the co-occurrence of two cardiometabolic diseases i.e., type 2 diabetes and CVD within a 20-year follow-up period in a sample of n=1,846 participants with available data. Results The median consumption level of UPFs was 26.6 (16.3) servings/week contributing to around 40% of participants total daily energy intake. Over the 20–year follow–up period, n=231 cases of cardiometabolic multimorbidity were recorded. Ranking from 1st tertile (lower intake– 11.8 mean servings/week) to 2nd tertile (23.3 mean servings/week) and 3rd tertile (44.7 mean servings/week) regarding the consumption level of UPF, 20-year cardiometabolic multimorbidity was 9.5%, 13.4% and 14.7% respectively. Multi-adjusted analysis revealed that one standard deviation (SD) increase in UPF intake (servings/week) or in contribution of UPFs to total energy intake (% total energy intake) was associated with 26% [Odds ratio (OR)=1.26, 95% Confidence Interval (95%CI) (1.17–1.85)] and 29% higher risk of cardiometabolic multimorbidity [OR=1.29, 95%CI (1.08–1.69)]. Among UPF subgroups, only in case of artificial and sugar-sweetened beverages [OR=1.06, 95%CI (1.02–1.13)] as well as spreads and sauces [OR=1.06, 95%CI (1.02–1.13)] a positive association was observed. In case of breads and cereals an inverse association was observed [OR=0.95, 95%CI (0.92–0.98)]. In the rest categories even if a positive trend was observed (all ORs&amp;gt;1) significance was not reached (all p-values&amp;lt;0.05). Conclusion A dose-response relationship between UPF consumption and elevated risk of cardiometabolic multimorbidity was emerged. However, the diverse categorization of UPFs accompanied by the contradicting associations revealed herein among the different subcategories of UPFs could imply the need to return to the evaluation of foods more on the basis of their nutritional role and less on the basis of their degree of processing. The nation context accompanied by specific dietary habits should also be taken into consideration.

Characteristics and outcomes of patients with a history of cancer enrolled in our prospective HFpEF registry

Abstract Background Along with the aging population, the incidence of concomitant heart failure with preserved ejection fraction (HFpEF) and cancer, is increasing. However, little is known about the typical characteristics of patients with both HFpEF and a history of oncologic disease. Aim We aimed to characterize the distinctive characteristics and outcomes of patients with a history of cancer within a prospective HFpEF registry. Methods We analyzed data from 491 unselected HFpEF patients from our tertiary university center between 2010 and 2022 and followed the patients until 2023. Laboratory parameters and comorbidities were assessed. Patients were categorized into those with and without a history of cancer, including various malignancies, survivors of childhood cancer, radiation therapy, with or without chemotherapy. Kaplan-Meier estimates were used to explore the association between cancer history, as well as previous radiotherapy, and a combined endpoint of heart failure hospitalization and/or all-cause death. Results In this analysis of 491 HFpEF patients, a total of 101 patients (21%); had a history of cancer [mean age 74±7 years; female 72 (72%), male 29 (29%)]. The median time from cancer diagnosis to the initial HFpEF visit was 7.0 years (IQR 13-0.5 years). The most prevalent primary cancer sites included the chest wall (32%) comprising 4 adenocarcinomas of the lung and 28 cases of breast cancer, followed by the gastric (28%), urogenital system (18%), hematologic and lymphatic system (16%), cancers located at the head and neck (5%) and endocrine malignancies (1%). Radiotherapy (39%) and chemotherapy (26%) were common. Notably, no significant differences were observed, between patients with or without a history of cancer, in terms of median NT-proBNP levels [1037 (IQR 416-2075) vs. 1060 pg/ml (IQR 462-2013)] and the frequency of key cardiovascular comorbidities (all p&amp;gt;0.05, see Table 1). Over the study period [median follow-up 50 months (IQR 18-76)], 64 (64%) of cancer patients met the combined endpoint, with no statistically significant difference in outcomes between HFpEF patients with and without a cancer history (log-rank p=0.222, see Figure 1). Furthermore, there was no significant difference in the combined endpoint between patients who had undergone radiotherapy and those without (log-rank p=0.162). Conclusion Our findings highlight a high coexistence of cancer and HFpEF, which can frequently occur after oncology therapies. The data suggest that the presence of a history of cancer or previous radiotherapy did not significantly impact overall outcomes in HFpEF patients compared to those without cancer during the study period. Further research is needed to characterize patients with both disease entities in detail. Due to modern cardiovascular therapy in a university and cardio-oncology clinic setting, outcomes for cancer patients appear better than expected.

Incidence of acute cardiovascular hospitalizations and association with hemodynamic biomarkers in cancer patients treated with Immune Checkpoint Inhibitor therapy

Abstract Background/Introduction Immune checkpoint inhibitors (ICI) have significantly improved outcomes for several malignancies. Despite these benefits, patients with cancer face an increased risk for the development of cardiovascular disease due to mutual risk factors, similar biological mechanisms, as well as cardiotoxic side effects of therapy. Therefore, there is a pressing need for effective risk stratification strategies. Purpose This study aimed to explore the association between NT-proBNP levels and the risk of acute cardiovascular hospitalizations and death in patients who receive ICI. Methods We used electronic health records of patients treated with ICI who had available baseline NT-proBNP levels at our hospital, a tertiary academic center, between January 2017 and July 2022. The primary outcome of interest was the composite of acute cardiovascular hospitalization or death. The associations between NT-proBNP and outcomes were analyzed using cox regression models adjusted for age, sex, serum creatinine, diabetes, HF, CAD, hypertension, AF, LDL-C, and CRP. Results In total, 550 patients (35% female, median age 65 yrs) were included in the study. The median NT-proBNP levels were 272 pg/mL (IQR 102-742 pg/mL) and 388 (71%) patients had NT-proBNP levels ≥125 pg/mL. During a median FU of 67 weeks, 190 patients (35%) died, and 103 CV hospitalizations occurred in 76 patients (14%). Compared with patients with NT-proBNP concentrations &amp;lt;125, those with NT-proBNP concentrations ≥125 pg/ml had significantly higher event rates of the combined endpoint (12-Month KM event rates: 38% vs 21%, P&amp;lt;0.001). After multivariable adjustment, NT-proBNP remained independently associated with an increased risk of cardiovascular hospitalization and death (Adjusted HR for 1-SD increase in log-transformed biomarker 1.64, 95% CI 1.24 to 2.14; Figure). Conclusion These data highlight NT-proBNP levels as a valuable marker for identifying patients at increased risk of cardiovascular complications during ICI therapy.

Tricuspid regurgitation in atrial fibrillation: correlation to left atrial myopathy and improvement post ablation

Abstract Background Atrial fibrillation (AF) closely correlates to left atrial (LA) myopathy, which in turn can cause functional mitral regurgitation (FMR). The correlation of LA myopathy to tricuspid regurgitation (TR) is still unknown. Data on the dynamic change of TR post AF ablation is still limited. Purpose We sought to investigate the correlation of LA myopathy to TR and furthermore if TR can be improved by AF ablation. Methods Consecutive patients presenting for first time AF ablation were prospectively enrolled. All patients underwent transthoracic echocardiography at baseline as well as 6 months after the ablation procedure. TR was graded as follows: minimal, mild, moderate and severe (I-IV). All study participants underwent high density bipolar voltagemaps prior to AF ablation to characterize the presence of atrial myopathy. Results Our final study cohort consisted of 143 patients (age 64±11 years, 47% female, 48% persistent AF). 15% had no, 21% minimal, 35% mild, 19% moderate and 9% severe TR, respectively. High density maps with 1325±736 mapping points and with an average bipolar voltage of 1.58±0.89mV were created. A significant decline of average LA bipolar voltage was obvious, when comparing patients without TR to any severity level of TR (p=0.015) (Figure 1), however there was no significant difference in LA bipolar voltage, when comparing different TR severity levels (Figure 1). After a follow up of 6 months a significant improvement of TR was observed (p&amp;lt;0.001) with a median level of improvement by one level. 27% had no, 21% minimal, 31% mild, 18% moderate and 2% severe TR, respectively. Conclusion In patients presenting for AF ablation TR closely correlates with LA myopathy according to decreased levels of LA bipolar voltage. AF ablation results in highly significant TR level improvement.

Predialysis central arterial waveform and blood pressure changes during hemodialysis

To investigate the predictive value of the central arterial waveform for intradialytic blood pressure (BP) change, a total of 152 hemodialysis patients (mean age 68 years) on a thrice-weekly hemodialysis schedule were enrolled, and at both the first and second session of the week, BP and central arterial waveform were measured every 30 min during hemodialysis. In both sessions, a 1-standard deviation increase in baseline subendocardial viability ratio (SEVR), an index of subendocardial perfusion, as well as in baseline systolic BP (SBP) was an independent predictor of maximum SBP decrease ≥ 30 mmHg during hemodialysis. When divided into four groups based on the respective median level of SEVR in the SBP ≥ median and SBP < median groups, intradialytic SBP change was different among the subgroups. Multiple logistic regression analysis revealed that, compared with the SBP < median; low SEVR group, the SBP < median; high SEVR group had lower risk, and the SBP ≥ median; low SEVR group had higher risk of SBP decrease ≥ 30 mmHg, but the risk did not differ from that in the SBP ≥ median; high SEVR group. Predialysis subendocardial perfusion evaluated by SEVR was associated with the maximum intradialytic BP decrease, and evaluation of the central arterial waveform could be used as complementary screening for intradialytic BP change.

Lipoprotein(a) levels and cholesterol efflux capacity: inverse association and impact on atherosclerosis in familial hypercholesterolemia patients on lipid-lowering therapy

Abstract Backgrounds Familial hypercholesterolemia (FH) patients have higher serum lipoprotein(a) (Lp(a)) levels than non-FH patients, and high Lp(a) levels raise atherosclerotic cardiovascular disease (ASCVD) risk 1). We previously reported that decreased cholesterol efflux capacity (CEC) is a risk marker for ASCVD in patients with statin-treated FH 2). Others have reported that Lp(a) interferes with the enhancement of ABCA1-mediated cholesterol efflux by plasminogen and that ABCA1-mediated CEC is lower in patients with Lp(a) &amp;gt;50 mg/dL. However, the association of CEC, not necessarily ABCA1-mediated, with Lp(a) is not clear and has not been studied in patients with FH. It is also unclear whether high Lp(a) and low CEC in patients with FH are associated with the severity of atherosclerosis. Purpose We examined whether Lp(a) levels are negatively associated with ABCA1-independent CEC in patients with FH receiving lipid-lowering therapy. We also examined the impact of the combination of high Lp(a) and low CEC on the presence of corneal arcus, Achilles tendon thickness, carotid intima-media thickness (IMT), and pre-existing ASCVD. Methods This cross-sectional study included 371 patients clinically diagnosed with FH receiving lipid-lowering therapy. CEC was measured in apolipoprotein B-depleted plasma and 3H-cholesterol-labeled J774.1 cells without cAMP-stimulated ABCA1 overexpression. Lp(a) was measured by enzymatic methods (Sekisui Medical, Tokyo, Japan) using an automated analyser. Achilles tendon thickness was measured by X-ray and carotid IMT by ultrasound. Results Mean age was 55±16 years, and 191 (51%) were women. The median serum Lp(a) level was 18.7 mg/dL, higher than the previously reported median level (13 mg/dL) in a Japanese population. One hundred nineteen patients (32%) had serum Lp(a) levels of 30 mg/dL or higher, and they had significantly lower CEC (P=0.0015). This negative association persisted after adjusting for age, sex, BMI, smoking status, serum LDL-cholesterol, serum triglycerides, and eGFR in a multiple linear regression model (beta-coefficient: -0.047, 95% CI: -0.075 - -0.019, P=0.0011). In addition, patients with both Lp(a) &amp;gt; 30 mg/dL and CEC lower than the median had a higher percentage of corneal arcus, thicker Achilles tendons, greater carotid IMT, and a higher prevalence of pre-existing ASCVD compared to patients with either or neither. Conclusions We found an inverse relationship between Lp(a) levels and CEC in FH patients receiving lipid-lowering therapy. Our results suggest that Lp(a) may also inhibit ABCA1-independent CEC, including passive cholesterol diffusion from peripheral cells. Furthermore, the combination of high Lp(a) and low CEC may be a residual risk for patients with FH receiving lipid-lowering therapy. Future studies are needed to determine whether agents that decrease Lp(a) levels will increase CEC and thereby resolve part of the residual ASCVD risk in FH.

Efficacy of Epoetin Alfa in Managing Symptomatic Anaemia in Low-Risk Myelodysplastic Syndromes: A Retrospective Analysis.

Background Myelodysplastic syndromes (MDS) are clonal myeloid disorders characterised by ineffective haematopoiesis, leading to anaemia that often requires dependence on red blood cell (RBC) transfusions. Epoetin alfa (Eprex®) is now a mainstay in the management of symptomatic anaemia in low-risk MDS patients, reducing transfusion dependence and improving the quality of life in this patient group. Objective This retrospective study aimed to assess the efficacy of epoetin alfa in treating symptomatic anaemia in low-risk MDS patients, focusing on transfusion independence and its relationship with baseline erythropoietin (EPO) levels and haemoglobin (Hb) response. Methods Data from 56 patients with low-risk MDS treated with epoetin alfa at Norfolk and Norwich University Hospital,Norwich, United Kingdom, between 2018 and 2023 were retrospectively analysed. Baseline EPO levels, transfusion history, Hb response, and the duration of transfusion independence were assessed. Statistical analyses were performed to evaluate the correlation between baseline characteristics and treatment outcomes. Results Among the patients, 98.2% had baseline EPO levels below the 500 IU/L threshold, with a median EPO level of 74.3 IU/L. Following an eight-week trial of 30,000 units of epoetin-alfa, 41.1% of patients showed improved Hb levels, 41.1% maintained stable Hb levels, and 17.9% experienced a decline. A significant correlation was found between lower baseline EPO levels (<250 IU/L) and a positive treatment response (p = 0.0065). Additionally, patients who required fewer transfusions before treatment had longer durations of transfusion independence (correlation coefficient = -0.40, p = 0.015). Dose escalation to 60,000 units provided a benefit to 53.3% of patients with initially stable Hb levels. The average duration of transfusion independence was 8.1 months, and patients with improved Hb levels had the longest periods of transfusion independence (p = 0.005). Conclusion Epoetin alfa is an effective therapy for managing symptomatic anaemia in low-risk MDS patients. This study highlights its efficacy and provides valuable predictive information, particularly showing that patients with lower baseline EPO levels are more likely to respond to treatment. While prior transfusion dependence did not significantly predict response to therapy in this cohort, it was associated with the duration of transfusion independence.

A study on the efficacy and safety of long-term adjusted low-dose gonadotropin-releasing hormone agonist therapy for uterine fibroids and adenomyosis.

To investigate the efficacy and safety of long-term adjusted low-dose gonadotropin-releasing hormone agonist therapy (GnRH agonist drawback therapy) with nafarelin acetate in patients with uterine fibroids and/or adenomyosis with menstrual symptoms. This single-center, retrospective, observational study initially included 118 patients with uterine fibroids and/or adenomyosis with menstrual symptoms who had received GnRH agonist (nafarelin acetate) drawback therapy for at least 7 months between 2010 and 2020. Blood hemoglobin level, maximum fibroid diameter, area of the corpus uteri, blood estradiol level, daily dosage of nafarelin acetate, and bone density in the lumbar spine and femoral neck were assessed before and after the treatment initiation. The median treatment period was 28 months. Menstruation had ceased in all patients. The median hemoglobin level significantly increased from 8.6 to 13.2 g/dL before treatment and at 12 months after the treatment initiation in patients with fibroids and from 8.8 to 13.3 g/dL in patients with adenomyosis, respectively. Although the treatment did not exert a significant shrinking effect on the fibroids and adenomyosis, an increase in their size was not observed in any patient. The initial dose of nafarelin acetate was 400 μg/day and was lowered to 130 μg/day at 12 months. Only 29 patients (25%) had an estradiol level <30 pg/mL. The average rate of bone density change over 6 months was -1.23% in the lumbar spine and -1.12% in the femoral neck in patients with fibroids and -1.06% in the lumbar spine and -0.14% in the femoral neck in patients with adenomyosis, which were lower than the previously reported rates. GnRH agonist drawback therapy was found to be useful for the long-term conservative treatment of uterine fibroids and adenomyosis. The treatment was safely and inexpensively performed with few adverse events.

Effect of Statins and Renin-Angiotensin-Aldosterone System Inhibitors on IL-6 Levels in COVID-19 Patients.

Background/Objectives: Severe clinical course and mortality from COVID-19 are mostly associated with increased concentrations of IL-6 and IL-10. Findings from clinical trials suggest that both statins and renin-angiotensin-aldosterone system inhibitors (RAASI) might have the potential to reduce unfavorable outcomes in patients with COVID-19. The aim of this study was to evaluate the effect of statins and RAASI on the cytokine concentrations in COVID-19 patients. Methods: SARS-CoV-2 infected patients were enrolled in this study, and demographic, clinical, and routine laboratory data were evaluated. Plasma cytokine levels were measured by multiplex assay. Results: COVID-19 patients with chronic cardiovascular diseases (CVD) had significantly lower median plasma IL-6 levels than COVID-19 patients with no co-morbidities (26 vs. 53 pg/mL, p = 0.021). COVID-19 patients with CVD who were taking statins had significantly lower median concentrations of IL-6 (21 vs. 44 pg/mL, p = 0.027), TNFα (21 vs. 39.5 pg/mL, p = 0.036), and IL-10 (19 vs. 25.5 pg/mL, p = 0.025) compared to COVID-19 patients with no CVD. In a binary logistic regression model, IL-6 was a significant variable, with an odds ratio value of 0.961 (95% CI 0.929-0.995). Regarding RAASI, only plasma IL-6 (22 vs. 44 pg/mL, p = 0.012) levels were found to be significantly lower in COVID-19 patients with CVD consuming these medications compared to patients who did not have any CVD. Conclusions: COVID-19 patients who had chronic cardiovascular co-morbidities and who were administered statins or RAASI had significantly lower concentrations of IL-6 than COVID-19 patients who did not have any co-morbidities. These findings suggest that the use of statins or RAASI may be of value in COVID-19 patients.

HIV replication and tuberculosis risk among people living with HIV in Europe: A multicohort analysis, 1983-2015.

HIV replication leads to a change in lymphocyte phenotypes that impairs immune protection against opportunistic infections. We examined current HIV replication as an independent risk factor for tuberculosis (TB). We included people living with HIV from 25 European cohorts 1983-2015. Individuals <16 years or with previous TB were excluded. Person-time was calculated from enrolment (baseline) to the date of TB diagnosis or last follow-up information. We used adjusted Poisson regression and general additive regression models. We included 272,548 people with a median follow-up of 5.9 years (interquartile range [IQR] 2.3-10.9). At baseline, the median CD4 cell count was 355 cells/μL (IQR 193-540) and the median HIV-RNA level 22,000 copies/mL (IQR 1,300-103,000). During 1,923,441 person-years of follow-up, 5,956 (2.2%) people developed TB. Overall, TB incidence was 3.1 per 1,000 person-years (95% confidence interval [CI] 3.02-3.18) and was four times higher in patients with HIV-RNA levels of 10,000 compared with levels <400 copies/mL in any CD4 stratum. CD4 and HIV-RNA time-updated analyses showed that the association between HIV-RNA and TB incidence was independent of CD4. The TB incidence rate ratio for people born in TB-endemic countries compared with those born in Europe was 1.8 (95% CI 1.5-2.2). Our results indicate that ongoing HIV replication (suboptimal HIV control) is an important risk factor for TB, independent of CD4 count. Those at highest risk of TB are people from TB-endemic countries. Close monitoring and TB preventive therapy for people with suboptimal HIV control is important.