The Selective NLRP3-inflammasome inhibitor MCC950 Mitigates Post-resuscitation Myocardial Dysfunction and Improves Survival in a Rat Model of Cardiac Arrest and Resuscitation

Purpose To investigate the effects of the selective NLRP3 inflammasome inhibitor MCC950 on post-resuscitation myocardial function and survival in a rat model of cardiopulmonary resuscitation (CPR). Methods Thirty-six Sprague Dawley rats were randomized into three groups: (1) MCC950, (2) control, and (3) sham. Each group consisted of a 6 h non-survival subgroup (n = 6) and a 48 h survival subgroup (n = 6). Ventricular fibrillation (VF) was induced and untreated for 6 min. CPR was initiated and continued for 8 min. Resuscitation was attempted with a 4 J defibrillation. MCC950 (10 mg/kg) or vehicle was administered via intraperitoneal injection immediately after the return of spontaneous circulation (ROSC). Myocardial function and sublingual microcirculation were measured after ROSC in the non-survival subgroups. Plasma levels of interleukin Iβ (IL-1β) and cardiac troponin I (cTnI) were measured at baseline and 6 h in the non-survival subgroups. Heart tissue was harvested to measure the NLRP3 inflammasome constituents, including NLRP3, apoptosis-associated speck-like protein (ASC), Caspase-1, and IL-1β. Survival duration and neurologic deficit score (NDS) were recorded and evaluated among survival groups. Results Post-resuscitation myocardial function and sublingual microcirculation were improved in MCC950 compared with control (p < 0.05). IL-1β and cTnI were decreased in MCC950 compared to control (p < 0.01). The MCC950 treated groups showed significantly reduced ASC, caspase-1, and IL-1β compared with the control group (p < 0.05). Survival at 48 h after ROSC was greater in MCC950 (p < 0.05) with improved NDS (p < 0.05). Conclusion Administration of MCC950 following ROSC mitigates post-resuscitation myocardial dysfunction and improves survival.

The Association Between Cardiovascular Autonomic Function and Changes in Kidney and Myocardial Function in Type 2 Diabetes and Healthy Controls

BackgroundThe mechanisms linking cardiovascular autonomic neuropathy, diabetic kidney disease and cardiovascular mortality in type 2 diabetes are widely unknown. We investigated the relationship between baseline cardiovascular autonomic function and changes in kidney and myocardial function over six years in patients with type 2 diabetes and healthy controls.MethodsPost-hoc analysis of a cohort study in 24 patients with type 2 diabetes and 18 healthy controls. Baseline determinants were cardiovascular autonomic reflex tests (heart rate response to: standing (30:15); deep breathing (E:I); and the Valsalva test) and time- and frequency-domain heart rate variability indices. Outcomes were changes in estimated glomerular filtration rate (eGFR), albuminuria, myocardial flow reserve (MFR) measured by cardiac 82Rb Positron emission tomography computed tomography (PET/CT), and coronary artery calcium score (CACS).ResultsMean age at inclusion was 61 ± 10 years and 36% were female. Mean follow up time was 6 ± 0 years. A lower response in heart rate to the Valsalva test (corresponding to weaker autonomic function) was associated with a larger decline in eGFR (p=0.04), but not significantly after adjustment for sex, baseline age, smoking status, systolic blood pressure, heart rate, HbA1c, body mass index and baseline eGFR (p=0.12). A higher baseline response in heart rate to standing (30:15) was associated with a larger decline in myocardial flow reserve in the unadjusted analysis (p=0.02) and after adjustment (p=0.02). A higher response in heart rate to the Valsalva maneuver was associated with a larger increase in CACS (p = 0.02), but the association became insignificant after adjustment (p = 0.16).ConclusionA lower response in heart rate to the Valsalva test was associated with a larger decline in kidney function, indicating that autonomic dysfunction may predict future loss of kidney function. However, we did not find any association between lower values in cardiovascular autonomic function at baseline and a worsening in albuminuria, myocardial function, or atherosclerotic burden.

Assessment of Left Ventricle Myocardial Function in Hypertensive Patients Using Three-Dimensional Speckle-Tracking Echocardiography (3D-STE)

Background: Increased myocardial fibrosis in hypertension leads to abnormalities in left ventricular diastolic function. 3D-speckle-tracking imaging (3D-STI) is a primary imaging modality used to detect early changes in the left ventricle (LV). The aim of this study was to assess the left ventricular myocardial function in hypertensive patients using 3D-speckle tracking imaging (3D-STI). Methods and Results: A case control, nonintervention, descriptive study was conducted in the Department of Ultrasound Diagnosis of Union Hospital of Tongji Medical College of Huazhong University of Science and Technology (Wuhan, Hubei, China). The study subjects included 64 patients with hypertension (HT) and, as control group, 44 normotensives. HT patients were divided into HT-I group (SBP of 130-139 mmHg or DBP of 80-89 mmHg, and HT-II group (SBP >140 mmHg or DBP >90 mmHg). In this study, LV geometry and function were assessed using conventional 2D- and 3D-echocardiography in a total of 108 consecutive subjects. LV volumes, global and regional strains were measured using 3D-STI. LV ejection fraction (LVEF) was in normal range in three groups, but in general, it slightly decreased in HT-II patients, compared with control and HT-I groups (62.5±2.1%, 68.0±2.2%, and 67.5±1.3%, respectively, P=0.00). Global systolic strain demonstrated a significant decrease in GLS, GCS, and GRS in the HT-II group, compared with control and HT-I groups. All regional strain parameters (longitudinal, circumferential, and radial) significantly decreased in HT-II patients, compared with control and HT-I groups. Conclusion: A significant deterioration of global LV systolic functions is found in hypertensive patients with well-preserved LVEF, especially in patients with hypertension stage II.

652 Myocardial work in patients undergoing transcatheter aortic valve implantation: clinical value and implications for outcome

Aims Non-invasive myocardial work (MW) quantification has emerged in the last years as an alternative echocardiographic tool for myocardial function assessment. This new parameter provides a less loading-dependent evaluation of myocardial performance through the combined assessment of global longitudinal strain (GLS) and non-invasive left ventricle (LV) pressures. The role of MW as a marker of cardiac dysfunction and reverse remodelling in patients with severe aortic stenosis (AS) after aortic valve implantation (TAVI) has not been adequately investigated. This study aims to evaluate MW indices as early echocardiographic markers of LV reverse remodelling within a month after TAVI and their prognostic value. Methods and results We conducted a single-centre prospective study, enrolling 70 consecutive patients (mean age 80.1 ± 5.5 years) with severe AS undergoing TAVI between 2018 and 2020, selected from the EffecTAVI registry. Exclusion criteria were prior valve surgery, severe mitral stenosis, permanent atrial fibrillation, left bundle branch block (LBBB) at baseline, and suboptimal quality of speckle-tracking image analysis. Echocardiographic assessment was performed before TAVI and at 30-day follow-up. Clinical, demographic, and resting echocardiographic data were recorded, including quantification of 2D global longitudinal strain (GLS), global work index (GWI), global constructive work (GCW), global wasted work (GWW), and global work efficiency (GWE). LV peak systolic pressure was estimated non-invasively from the sum of systolic blood pressure and trans-aortic mean gradient. One month after the procedure, there was a significant improvement of LV GLS (−17.94 ± 4.24% vs. −19.35 ± 4.31%, before and after TAVI respectively, P = 0.002), as well as a significant reduction of GWI (2430 ± 586 mmHg% vs. 1908 ± 472 mmHg%, P &lt; 0.001), GCW (2828 ± 626 mmHg% vs. 2206 ± 482 mmHg%, P &lt; 0.001), and GWW (238 ± 207 mmHg% vs. 171 ± 118 mmHg%, P = 0.006). Conversely, MWE did not significantly change early after intervention (90.53 ± 6.05% vs. 91.45 ± 5.05%, P = 0.204). After TAVI, 30 patients (42.8%) developed LV dyssynchrony due to LBBB or pacemaker implantation. When the population was divided according to the presence or absence of LV dyssynchrony at 30-day follow-up, a significant reduction in GWW was found only in those without dyssynchrony (244 ± 241 vs. 141 ± 110 mmHg% with and without dyssynchrony respectively, P = 0.002). Consistently, in this subgroup, MWE significantly improved post-TAVI (90 ± 7 vs. 93 ± 5%, P = 0.002), while a trend of MWE reduction was observed in patients who developed dyssynchrony post-TAVI (91 ± 4 vs. 89 ± 5%, P = 0.164). In the overall population, a baseline value of MWE&lt; 92% was associated with an increased rate of cardiovascular events (composite of all-cause death and rehospitalization for heart failure) at 1-year follow-up (22.2 vs. 3.1%, long rank, P = 0.016). Conclusions In patients with severe AS undergoing TAVI a significant reduction of GWW and improvement of MWE can be detected only in those who did not develop LV dyssynchrony. In this setting, MWE lower than 92% at baseline is associated with poor outcome. Thus, MWE could represent an alternative tool for myocardial function assessment in patients receiving TAVI.

799 Biventricular dysfunction and lung congestion in athletes on anabolic androgenic steroids: a speckle tracking and stress lung echocardiography analysis

Aims The real effects of the chronic consumption of anabolic–androgenic steroids (AAS) on cardiovascular structures are subjects of intense debate. Aim of the study was to detect by speckle tracking echocardiography (STE) right ventricular (RV) and left ventricular (LV) dysfunction at rest and during exercise stress echocardiography (ESE) in athletes abusing AAS. Methods and results 115 top-level competitive bodybuilders were selected (70 males), including 65 athletes misusing AAS for at least 5 years (users), 50 anabolic-free bodybuilders (non-users), compared to 50 age- and sex-matched healthy sedentary controls. Standard Doppler echocardiography, STE analysis, and lung ultrasound at rest and at peak supine-bicycle ESE were performed. Athletes showed increased LV mass index, wall thickness, and RV diameters compared with controls, whereas LV ejection fraction was comparable within the groups. LA volume index, LV and RV strain, and LV E/Em were significantly higher in AAS users. Users showed more B-lines during stress (median 4.4 vs. 1.25 in controls and 1.3 in non-users, P &lt; 0.01 vs. users). By multivariable analyses, LV E/Ea (beta coefficient = 0.35, P &lt; 0.01), PASP (beta = 0.43, P &lt; 0.001) at peak effort, and number of weeks of AAS use per year (beta = 0.45, P &lt; 0.001) emerged as the only independent determinants of resting RV lateral wall peak systolic two-dimensional strain. In addition, a close association between resting RV myocardial function and VO2 peak during ESE was evidenced (P &lt; 0.001), with a powerful incremental value with respect to clinical and standard echocardiographic data. Conclusions STE represents a promising technique to assess RV myocardial function in athletes abusing steroids. AAS users showed a more impaired RV deformation, closely associated with reduced functional capacity during physical effort, and—during exercise—more pulmonary congestion.