Association of inflammatory biomarkers and disease activity with subclinical myocardial dysfunction in psoriatic arthritis.

We examined the role of adipokines and pro-inflammatory cytokines in psoriatic arthritis-associated subclinical myocardial dysfunction, and the relationship between these variables and psoriatic arthritis (PsA) disease activity. Fifty-five PsA patients without cardiovascular risk factors and 25 controls underwent standard and speckle tracking echocardiography with global longitudinal strain (GLS) calculated. Standard anthropometric data and Disease Activity in Psoriatic arthritis (DAPSA) scores were recorded, with low disease activity defined as DAPSA ≤ 14 and moderate and high disease activity DAPSA > 14. Standard biochemical tests, adiponectin, resistin, leptin, tumor necrosis factor (TNF) alfa, interleukin 17 A (IL-17A), B lymphocyte chemoattractant (BLC), and monokine induced by intereferon gamma (MIG) were analyzed. Median age was 53.0 (46.0-61.0), median PsA duration 6.0 (4.0-13.0) years and median DAPSA score 25.5 (13.0-41.5). Lower GLS, tricuspid annular plane systolic excursion (TAPSE) and left ventricular ejection fraction (LVEF) were found in moderate and high PsA disease activity compared to low PsA disease activity and controls. PsA patients with GLS < 20 had higher body mass index (BMI), DAPSA score and uric acid levels, and lower adiponectin levels. Although patients with GLS < 20 had higher IL-17A levels, it was not statistically significant (P = 0.056). However, when we included healthy controls and analyzed differences based on a GLS cut-off of 20% in the entire population, the difference in IL-17A became statistically significant, 0.17 pg/mL (0.06-0.32) vs. 0.43 pg/mL (0.23-0.65), P = 0.017. The association between DAPSA score and GLS and IL-17 remained significant in multivariate analysis. Moreover, the association between GLS and IL-17 and adiponectin was significant after adjustment for age and BMI. Patients with moderate and high PsA disease activity have reduced myocardial function, lower adiponectin, and higher IL-17A levels.

Left Ventricular Systolic Function After 3 Months of SGLT2 Inhibitor Therapy in Heart Failure Patients with Reduced Ejection Fraction.

Not much is known about the effects of sodium-glucose cotransporter 2 inhibitors (SGLT2i) on echocardiographic parameters of left ventricular (LV) systolic function in patients with heart failure and reduced ejection fraction (HFrEF).We prospectively included 59 outpatients with HFrEF: 41 patients received SGLT2i with OMT (SGLT2i+ group), whereas eighteen patients received OMT without SGLT2i (SGLT2i- group). Myocardial work index (MWI), 3D ejection fraction (3D LVEF), and global longitudinal strain (GLS) were measured at baseline and after 3 months following treatment. At 3-month follow-up, the SGLT2i+ group showed significantly greater improvement in MWI than the SGLT2i- group. In both groups, there was a significant improvement in 3D LVEF and LV GLS, circulating NT-proBNP levels, and NYHA functional class, with significantly greater improvement in the SGLT2i+ group.In conclusion, the addition of SGLT2i to fully optimized background medical therapy resulted in a greater improvement of LV systolic function among outpatients with HFrEF.

Impact of SGLT2 Inhibitor Therapy on Right Ventricular Function in Patients with Heart Failure and Reduced Ejection Fraction.

Background: The impact of sodium-glucose cotransporter-2 inhibitors (SGLT2is) in addition to optimal medical therapy (OMT) on the right ventricular (RV) systolic function using advanced echocardiographic analysis among outpatients with heart failure and a reduced ejection fraction (HFrEF) has thus far been poorly investigated. Methods: This was a single-center, prospective, single-blinded study in which an echocardiographic expert was blinded to the allocation of the treatment. A total of 36 outpatients with HFrEF were randomized to either OMT or OMT+SGLT2i. Both groups underwent an echocardiographic examination of the RV systolic function at the baseline and at the 3-month follow-up (3mFU). Results: The patients in both groups did not significantly differ with respect to the relevant baseline comorbidities, therapy, and clinical characteristics. The patients receiving OMT+SGLT2i showed a significant improvement from the baseline to the 3mFU in all the measured RV echocardiographic parameters, while for the OMT group, a significant improvement after the 3mFU was observed for TAPSE and s'. The mean percent change from the baseline to the 3mFU was significant when comparing OMT+SGLT2i to the OMT group concerning RV FWS (+91% vs. +28%, p = 0.039), TR maxPG (-27% vs. +19%, p = 0.005), and TR Vmax (-17% vs. +13%, p = 0.008), respectively. Conclusions: Adding SGLT2i to OMT in patients with HFrEF resulted in a greater improvement in the RV systolic function from the baseline to the 3mFU compared to the OMT alone.

Circulating sST2 and catestatin levels in patients with acute worsening of heart failure: a report from the CATSTAT-HF study.

AIMS: Soluble suppression of tumourigenicity 2 (sST2) and catestatin (CST) reflect myocardial fibrosis and sympathetic overactivity during the acute worsening of heart failure (AWHF). We aimed to determine serum levels and associations of sST2 and CST with in-hospital death as well as the association between sST2 and CST among AWHF patients. METHODS AND RESULTS: A total of 96 AWHF patients were consecutively enrolled, while levels of sST2 and CST were determined and compared between non-survivors and survivors. Predictive values of sST2 and CST for in-hospital death were determined by the penalized multivariable Firth logistic regression. The diagnostic ability of sST2 and CST for in-hospital death was assessed by the receiver operating characteristic analysis and examined with respect to the N-terminal pro-brain natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin I, and C-reactive protein. The in-hospital death rate was 6.25%. Serum sST2 and CST levels were significantly higher among non-survivors than survivors [146.6 (inter-quartile range, IQR 65.9-156.2) vs. 35.3 (IQR 20.6-64.4) ng/mL, P < 0.001, and 19.8 (IQR 9.9-28.0) vs. 5.6 (IQR 3.4-9.8) ng/mL, P < 0.001, respectively]. Both sST2 and CST were independent predictors of in-hospital death [Firth coefficient (FC) 6.00, 95% confidence interval (CI), 1.48-15.20, P = 0.005, and FC 6.58, 95% CI 1.66-21.78, P = 0.003, respectively], while NT-proBNP was not a significant predictor (FC 1.57, 95% CI 0.51-3.99, P = 0.142). In classifying non-survivors from survivors, sST2 provided area under the curve (AUC) of 0.917 (95% CI 0.819-1.000, P < 0.001) followed by CST (AUC 0.905, 95% CI 0.792-1.000, P < 0.001), while NT-proBNP yielded AUC of 0.735 (95% CI 0.516-0.954, P = 0.036). High-sensitivity cardiac troponin I and C-reactive protein were not found as significant classifiers of in-hospital death (AUC 0.719, 95% CI 0.509-0.930, P = 0.075, and AUC 0.682, 95% CI 0.541-0.822, P = 0.164, respectively). Among survivors, those with sST2 serum levels ≥35 ng/mL had significantly higher CST levels, compared with those with sST2 < 35 ng/mL (9.05 ± 5.17 vs. 5.06 ± 2.76 ng/mL, P < 0.001). Serum sST2 levels positively and independently correlated with CST levels in the whole patient cohort (ß = 0.437, P < 0.001). CONCLUSIONS: Elevated sST2 and CST levels, reflecting two distinct pathophysiological pathways in heart failure, might indicate impending clinical deterioration among AWHF patients during hospitalization and facilitate prognosis beyond traditional biomarkers regarding the risk of in-hospital death (CATSTAT-HF ClinicalTrials.gov Number NCT03389386).

Right Ventricular Free Wall Strain and Congestive Hepatopathy in Patients with Acute Worsening of Chronic Heart Failure: A CATSTAT-HF Echo Substudy.

Right ventricular (RV) function is an important predictor of prognosis in patients with heart failure. However, the relationship of the RV free wall longitudinal strain (RV FWS) and the degree of hepatic dysfunction during the acute worsening of heart failure (AWHF) is unknown. We sought to determine associations of RV FWS with laboratory liver function tests and parameters of RV function including tricuspid annular plane systolic excursion (TAPSE), RV fractional area change (RV FAC), maximal tricuspid jet velocity (TR Vmax), RV S' velocity, and estimated RV systolic pressure (RVSP). A total of 42 AWHF patients from the CATSTAT-HF study were stratified in two groups by the RV FWS median (-16.5%). Patients < RV FWS median had significantly prolonged international normalized ratio (INR; p = 0.002), increased total bilirubin (p < 0.001) and alkaline phosphatase (ALP; p = 0.020), and decreased albumin (p = 0.005) and thrombocytes (p = 0.017) compared to patients > RV FWS median. RV FWS independently correlated to total bilirubin (ß = 0.457, p = 0.004), ALP (ß = 0.556, p = 0.002), INR (ß = 0.392, p = 0.022), albumin (ß = -0.437, p = 0.013), and thrombocytes (ß = -404, p = 0.038). Similarly, TAPSE, RV FAC, and RV S' significantly correlated with RV FWS. In conclusion, RV impairment, reflected in reduced RV FWS, is independently associated with a higher degree of hepatic dysfunction among patients with AWHF (CATSTAT-HF ClinicalTrials gov number, NCT03389386).

Catestatin in Acutely Decompensated Heart Failure Patients: Insights from the CATSTAT-HF Study.

The role of catestatin (CST) in acutely decompensated heart failure (ADHF) and myocardial infarction (MI) is poorly elucidated. Due to the implicated role of CST in the regulation of neurohumoral activity, the goals of the study were to determine CST serum levels among ninety consecutively enrolled ADHF patients, with respect to the MI history and left ventricular ejection fraction (LVEF) and to examine its association with clinical, echocardiographic, and laboratory parameters. CST levels were higher among ADHF patients with MI history, compared to those without (8.94 ± 6.39 vs. 4.90 ± 2.74 ng/mL, p = 0.001). CST serum levels did not differ among patients with reduced, midrange, and preserved LVEF (7.74 ± 5.64 vs. 5.75 ± 4.19 vs. 5.35 ± 2.77 ng/mL, p = 0.143, respectively). In the multivariable linear regression analysis, CST independently correlated with the NYHA class (ß = 0.491, p < 0.001), waist-to-hip ratio (WHR) (ß = -0.237, p = 0.026), HbA1c (ß = -0.235, p = 0.027), LDL (ß = -0.231, p = 0.029), non-HDL cholesterol (ß = -0.237, p = 0.026), hs-cTnI (ß = -0.221, p = 0.030), and the admission and resting heart rate (ß = -0.201, p = 0.036 and ß = -0.242, p = 0.030), and was in positive association with most echocardiographic parameters. In conclusion, CST levels were increased in ADHF patients with MI and were overall associated with a favorable cardiometabolic profile but at the same time reflected advanced symptomatic burden (CATSTAT-HF ClinicalTrials.gov number, NCT03389386).

2D speckle tracking echocardiography of the right ventricle free wall in SCUBA divers after single open sea dive.

The presence of circulating gas bubbles and their influence on pulmonary and right heart hemodynamics was reported after uncomplicated self-contained underwater breathing apparatus (SCUBA) dive(s). Improvements in cardiac imaging have recently focused great attention on the right ventricle (RV). The aim of our study was to evaluate possible effects of a single air SCUBA dive on RV function using 2D speckle tracking echocardiography in healthy divers after single open sea dive to 18 meters of seawater, followed by bottom stay of 47 minutes with a direct ascent to the surface. Twelve experienced male divers (age 39.5 ± 10.5 years) participated in the study. Echocardiographic assessment of the right ventricular function (free wall 2 D strain, tricuspid annular planes systolic excursion [TAPSE], lateral tricuspid annular peak systolic velocity [RV s`] and fractional area change [FAC]) was performed directly prior to and 30, 60, 90 and 120 minutes after surfacing. Two-dimensional strain of all three segments of free right ventricular wall showed a significant increase in longitudinal shortening in post-dive period for maximally 26% (basal), 15.4% (mid) and 16.3% (apical) as well as TAPSE (11.6%), RV FAC (19.2%), RV S` (12.7%) suggesting a rise in systolic function of right heart. Mean pulmonary arterial pressure (mean PAP) increased post-dive from 13.3 mmHg to maximally 23.5 mmHg (P = .002), indicating increased RV afterload. Our results demonstrated that single dive with significant bubble load lead to increase in systolic function and longitudinal strain of the right heart in parallel with increase in mean PAP.

Early Changes in Platelet Size and Number in Patients with Acute Coronary Syndrome.

A strong relationship exists between acute coronary syndrome (ACS) and platelets (PLTs) volume. Mean platelet volume (MPV) is a parameter of PLT functions and a marker for increased PLT activation. The aim of this study was to determine early changes in number of total PLT and MPV in different manifestation of ACS and to find out predictive value of MPV in the spectrum of ACS. This was a prospective study. One hundred thirty-four ACS patients were enrolled, 76 of them finished the study. PLT and MPV in patients with unstable angina, non-ST elevation, and ST elevation myocardial infarctions were determined on arrival and 1, 3, 72 hours, and 7 days after the admission to hospital. There was decrease in PLT and MPV in all three groups after 3 hours of arrival in hospital in comparison with admission values. In the later time period (72 hours and 7 days), there was an increase in PLT and MPV only in patients with acute myocardial infarction (AMI). We have revealed completely new dynamics in early changes in MPV and PLT count in patients with AMI. Biphasic changes were found in early phase after admission to the hospital. Fast response in these parameters raises new questions about their origin.

Diving and pulmonary physiology: Surfactant binding protein, lung fluid and cardiopulmonary test changes in professional divers.

Alteration of breathing pattern ranging from an increase of respiratory rate to overt hyperventilation during and after SCUBA diving is frequently reported and is associated with intrathoracic fluid overload. This study was undertaken to assess breathing efficiency after diving and the association with damage of alveolar cells. Ventilation efficiency (VE/VCO2) during maximal cardiopulmonary exercise test (CPET) before and 2h after a standard protocol dive has been analyzed in twelve professional males divers (39.5±10.5years). Furthermore, within 30min from surfacing, subjects underwent blood sample for surfactant derived proteins (SPs) determination, while thoracic ultrasound was performed at 30, 60, 90 and 120min. Dive consisted in a single quick descend to 18m of sea water, a 47min bottom stay and a direct ascent to the surface. CPET showed a preserved exercise performance with an increase of VE/VCO2 after diving (21.4±2.9 vs. 22.9±3.3, p<0.05). Mature SP-B increased while other SPs were unchanged. Ultrasound lung comets (ULC) were high in the first post-dive evaluation with a significant, but not complete, progressive reduction at 120min after surfacing. In conclusion we showed that, after a single dive, lung fluid increased with an increase of ventilation inefficiency and of the mature form of SP-B.

Characterization of blood flow through intrapulmonary arteriovenous anastomoses and patent foramen ovale at rest and during exercise in stroke and transient ischemic attack patients.

OBJECTIVES: We determined whether stroke and/or TIA subjects have exercise-induced blood flow through intrapulmonary arteriovenous anastomoses (QIPAVA ) and/or patent foramen ovale (QPFO ) and a genetic predisposition for ischemic stroke. METHODS: Twenty-eight stroke and/or TIA subjects (33-63 years old) underwent transthoracic saline contrast echocardiography concomitant with transcranial Doppler to detect QIPAVA and QPFO at rest and during supine exercise with and without breathing 100% O2 . We also examined genetic polymorphisms in FV Leiden (G1691A; rs6025), factor II (FII) prothrombin (G20210A; rs1799963), methylene tetrahydfropholate reductase (C677T, rs1801133), and plasminogen-activator inhibitor-1 (PAI-1) (4G/5G; rs1799889) and angiotensin-converting enzyme (ACE; I/D, rs4646994) in 24/28 subjects. RESULTS: No subject without PFO had QIPAVA at rest (n=17), but 12/17 did with exercise. All PFO subjects had QPFO at rest (n=11) and 7/11 had either QIPAVA or QPFO with exercise. Breathing 100% O2 during exercise reduced or eliminated left heart contrast in all subjects. Gene analyses revealed that 15/24 patients were either heterozygous or homozygous for methylenetetrahydrofolate reductase gene polymorphism; 4G/4G and 4G/5G genotypes of plasminogen-activator inhibitor-1 were present in 7/24 and 13/24 patients, respectively; polymorphisms of ACE D/D genotype were present in 6/24 and I/D in 14/24 patients. Having both I/D and 4G/4G genotypes was more prevalent in PFO+ subjects (P=.03), and there was a trend (P=.06) for PFO- subjects to have a greater D/D genotype prevalence. CONCLUSIONS: Novel genetic predispositions reported here in PFO subjects should be investigated further in larger stroke and/or TIA patient datasets.