Class III-IV Research Articles

Prevalence and prognostic value of different iron deficiency definitions in light chain cardiac amyloidosis patients.

Research on iron deficiency (ID) in patients with light chain cardiac amyloidosis (AL-CM) has been limited in previous studies. The purpose of this study was to investigate the prevalence and its association with prognosis of ID based on different definitions in patients with AL-CM. Three different ID definitions were applied: (1) serum ferritin concentration of <100ng/mL, or 100-299ng/mL with transferrin saturation (TSAT)<20% (according to guidelines on heart failure), (2) TSAT<20% and (3) serum iron <13μmol/L. The primary outcome measure was all-cause mortality. Prevalence and outcomes of various ID definitions were evaluated among patients diagnosed with AL-CM at Heart Failure Center, Fuwai Hospital between September 2017 and October 2023. Overall, 149 patients were included with a mean age of 60.71±10.11years, of whom 60 (40.3%) patients were female, 127 (85.2%) patients were in New York Heart Association (NYHA) class III-IV and 136 (91.3%) patients were in the revised Mayo 2012 stage III-IV. Assessments of iron biomarkers revealed the following results: median ferritin levels were 183.68ng/mL (interquartile range [IQR] 95.48, 339.01), median TSAT was 21.80% (IQR 16.34, 29.48), and median serum iron was 10.87μmol/L (IQR 7.38, 13.71). Serum iron were highly correlated with TSAT (r=0.85, P<0.0001). Depending on the definition used, 63 (42.3%) patients, 61 (40.9%) patients and 105 (70.5%) patients were defined as ID, respectively (P<0.0001). ID defined by TSAT and serum iron was associated with the primary outcome [hazard ratio (HR) 2.14, 95% confidence interval (CI) 1.36-3.37, P<0.001, and HR 2.16, 95% CI (1.23-3.80), P<0.01], but the same association was not seen with the guideline definition of ID [HR 1.39, 95% CI (0.88-2.18), P=0.158]. In the multivariable model adjusting for age, gender, haemoglobin, and revised 2012 Mayo staging, the predictive value of TSAT<20% [adjusted HR 2.49, 95% CI (1.54-4.05), P<0.001] and serum iron<13μmol/L [adjusted HR 2.24, 95% CI (1.23-4.09), P<0.01] remained. Different definitions of ID yield inconsistent results in terms of prevalence and prognosis. ID, as defined by TSAT<20% or serum iron<13μmol/L, rather than the guideline definition, emerged as an independent predictor of all-cause mortality in patients with AL-CM.

Limited or Lasting: Is Preoperative Weight Loss as Part of Prehabilitation Maintained after Open Ventral Hernia Repair?

Obesity is directly correlated with wound complications and recurrence following open ventral hernia repair (OVHR). Preoperative weight loss (WL) mitigates these risks, improves overall health, and reduces intraabdominal volume. For patients successful in losing weight, it is unclear whether this WL is maintained. A prospective, single-institution hernia database was queried for patients with a BMI≥25kg/m2, who were requested to lose weight and lost a minimum of 10lbs preoperatively. Patients' weight was examined at two timepoints: postoperative appointment 6months-1year and their most recent documented weight. Of 256 included patients, average age was 58.2±11.2 years, 30.5% were diabetic, and 67.9% were ASA class III-IV. At initial consultation, average BMI was 38.2±6.6kg/m2 and 34.0±5.8kg/m2 at time of surgery. Average preoperative WL was 26.1±17.1lbs (10-120lbs) over 10.0±13.6 months.At the first postoperative timepoint, average BMI was 33.6±5.8kg/m2, and patients lost an additional 1.8±16.2lbs over 8.4±9.0 months after surgery. At 42.0±36.2 months postoperatively, patients gained an average of 2.0±27.1lbs, for a net WL of 24.0±31.9lbs from consultation.After surgery, 47.3% of patients continued WL for an additional 18.6±26.4lbs (total net WL: 44.7lbs) and decreased BMI by 2.5±3.6kg/m2; 0.8% maintained their same weight; 22.3% gained back less than half of preoperative WL, totaling 70.3% of patients with long-term optimization. Prehabilitation-induced WL averaged 26lbs. With 3.5years follow-up, patients weighed an average of 24lbs less than their initial consult weight. Nearly half of patients continued WL postoperatively, and more than 70% maintained at least half of their WL, demonstrating longevity to preoperative optimization.

Risk factors for the delayed discharge from anesthesia intensive care unit: a single-center retrospective study

BackgroundA single-center retrospective study was designed to investigate the risk factors associated with delayed discharge from the Anesthesia Intensive Care Unit (AICU).MethodsThis retrospective study involved patients admitted in the AICU from January 2017 to December 2022. Risk factors for the delayed discharge from the AICU were analyzed by the binary multivariate logistic regression analysis. Nomogram was constructed to predict the risk of delayed discharge from AICU. The performance of the nomogram was assessed using the receiver operating characteristic curve and calibration curve. A decision curve analysis was also performed to determine the net benefit threshold of prediction.ResultsA total of 14,338 patients admitted in the AICU were retrospectively recruited, involving 9,271 males and 5,067 females. The incidence of delayed discharge from the AICU in the cohort was 1.54% (221/14,338). Binary multivariate logistic regression analysis showed that younger than 18 years or older than 64 years, the American Society of Anesthesiologists physical status of class III-IV, body mass index of less than 18 kg/m2 or greater than 25 kg/m2, preoperative complications, emergency surgeries and intraoperative massive hemorrhage were risk factors for the delayed discharge from an AICU. We utilized nomograms to visually express data analysis results. Based on receiver operating characteristic analysis, calibration plots, and decision curve analysis, we concluded that the nomogram model exhibited excellent performance. Patients undergoing spine surgeries suffered from the highest proportion of delayed discharge from the AICU, followed by those receiving orthopedic and vascular surgeries. Postoperative hemorrhage was the major cause of delayed discharge from an AICU, followed by septic shock, hypoperfusion and pulmonary insufficiency.ConclusionThe incidence of delayed discharge from the AICU in a single-center tertiary hospital is 1.54%. It is influenced by various risk factors, including age, ASA physical status classification, BMI, preoperative complications, type of surgery and intraoperative blood loss. The nomogram model exhibits excellent performance.Trial registrationThe single-center retrospective study was approved by the Ethics Committee of Nanjing Drum Tower Hospital (No. 2021-563-01, Data: 22 November 2021) and registered on the Chinese Clinical Trial Registry (No. ChiCTR2300078251, Data: 01 December 2023).

Lymphatic Drainage in Patients with Heart Failure: A Feasibility Study.

Lymphatic dysfunction contributes to congestion and end-organ damage in heart failure (HF), yet current therapies do not directly target lymphatic congestion. Thoracic duct (TD) drainage offers a novel approach to address this gap. This multicenter feasibility study evaluated the safety and feasibility of minimally invasive TD drainage in patients with HF. Four patients with New York Heart Association class II-IV HF and fluid overload underwent fluoroscopy-guidedTD access via cervical, abdominal, or transvenous brachial approaches. Lymph was drained by gravity for up to 3 hours, and hemodynamic changes were measured. TD drainage was successful in all patients, with a mean lymph output of 430 mL. Mean reductions in right atrial and pulmonary capillary wedge pressures were 4 mmHg and 1.5 mmHg, respectively. No major adverse events occurred. TD drainage appears feasible and safe, with potential decongestive benefits. Larger studies are needed to confirm its role in HF management.

Serum uric acid, renal function and prognosis in patients with chronic heart failure and reduced ejection fraction. Insights from the Italian Network on Heart Failure.

The role of hyperuricemia on short-term clinical prognosis in outpatients with heart failure and reduced ejection fraction (HFrEF) has few investigations and inconclusive results. We evaluated the prognostic impact of serum uric acid (SUA) on short-term clinical outcome among ambulatory patients with chronic HFrEF enrolled in a nationwide cardiology registry, stratified by the presence of chronic renal dysfunction (CKD). 2246 outpatients with LVEF ≤40%, vital status at 1-year follow-up known, and with SUA and creatinine available were stratified accordingly to SUA tertiles (≤5.6 5.7-7.3, >7.3mg/dl) and by CKD as defined by an estimated glomerular filtration rate<60ml/min/1.73m2. Patients in the 2nd and 3rd SUA tertile were older, more symptomatic (NYHA class III-IV), with a lower EF, higher creatinine and heart rate. They had more commonly atrial fibrillation and CKD. At 1-year follow-up, patients in the 2nd and 3rd SUA levels tertile had an increased risk of cardiovascular death and/or HF hospitalization than those in the first tertile (HR 1.72 95% CI 1.26-2.35, and HR 2.20 95% CI 1.63-2.97, respectively). After multivariable adjustment, SUA was no longer associated with adverse outcome in the overall cohort. When the multivariable analysis was separately performed in patients with or without CKD, SUA was independently associated with cardiovascular death/HF hospitalization (p=0.02) only in the latter group. Mildly to moderately elevated SUA levels are associated to one-year survival in outpatients with HFrEF, but hyperuricemia resulted an independent marker of outcome only in patients without CKD.

The Use of External Beam Radiation Therapy for Heterotopic Ossification Prophylaxis After Surgical Fixation of Acetabular Fractures: A Randomized Controlled Trial.

To determine the effect of external beam radiation (XRT) on preventing severe heterotopic ossification (HO) after acetabular surgery. Randomized controlled trial. Two level I academic trauma centers. Patients with an acetabular fracture (OTA/AO type 62) surgically treated through a posterior or combined anterior and posterior approach. Radiographic HO was determined using Brooker Classification at the last follow-up. The primary outcome was severe HO (Brooker classes III-IV). The secondary outcome was any HO (Brooker classes I-IV). The incidence of radiographic HO was compared between patients who did and did not undergo postoperative XRT. The results were analyzed in both an intention-to-treat (randomized to XRT) and as-treated (received XRT) basis. Severe HO occurred in 3 of 54 (6%) patients randomized to XRT and 9 of 50 (18%) patients randomized to no XRT (odds ratio 0.24, 95% confidence interval, 0.05 to 0.94; P = 0.05). Any HO occurred in 10 (19%) patients assigned to XRT and 17 (34%) patients in the no XRT control group (odds ratio 0.39; 95% confidence interval, 0.13 to 1.05; P = 0.07). The findings of this dual-center randomized controlled trial suggest that XRT after acetabular surgery significantly reduced the odds of severe HO compared with patients who did not receive XRT. These results can help guide shared decision making between surgeons and patients regarding the use of XRT for HO prophylaxis. Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

Safety and efficacy of satralizumab in patients with generalised myasthenia gravis (LUMINESCE): a randomised, double-blind, multicentre, placebo-controlled phase 3 trial.

Evidence from preclinical studies suggests that IL-6 signalling has the potential to modulate immunopathogenic mechanisms upstream of autoantibody effector mechanisms in patients with generalised myasthenia gravis. We aimed to assess the safety and efficacy of satralizumab, a humanised monoclonal antibody targeting the IL-6 receptor, in patients with generalised myasthenia gravis. LUMINESCE was a randomised, double-blind, placebo-controlled, multicentre, phase 3 study at 105 sites, including hospitals and clinics, globally. Eligible patients were aged 12 years and older, with seropositive generalised myasthenia gravis (autoantibodies to the acetylcholine receptor [AChR-IgG], muscle-specific kinase [MuSK-IgG], or low-density lipoprotein receptor-related protein 4 [LRP4-IgG]), a Myasthenia Gravis Foundation of America severity class II-IV, a Myasthenia Gravis Activities of Daily Living (MG-ADL) score of 5 or more (non-ocular contribution >50%), and use of stable background therapy. Patients were randomly assigned (1:1) with a permuted-block randomisation method to receive subcutaneous satralizumab (120 mg for bodyweight ≤100 kg; 180 mg for bodyweight >100 kg) or placebo at weeks 0, 2, 4, and every 4 weeks thereafter until week 24. Randomisation was stratified according to background therapy, autoantibody type, and geographical region. The primary efficacy endpoint was mean change from baseline in total MG-ADL score at week 24 in the modified intention-to-treat population (all randomised AChR-IgG-positive patients who completed at least one post-baseline MG-ADL assessment). Safety was assessed in all randomly assigned patients who received at least one dose of study drug. The open-label extension was terminated early because of the sponsor's decision to halt further development of satralizumab for treatment of generalised myasthenia gravis. This trial is registered with ClinicalTrials.gov, NCT04963270, and EudraCT, 2020-004436-21. Between Oct 19, 2021, and Aug 15, 2023, 188 patients were randomly assigned to satralizumab (n=96) or placebo (n=92). 166 AChR-IgG-positive patients (80 in the placebo group and 86 in the satralizumab group) were included in the modified intention-to-treat population. At week 24, statistically significant yet small improvements in MG-ADL score were observed with satralizumab versus placebo (adjusted mean -3·59, 95% CI -4·15 to -3·02 vs -2·57, -3·25 to -1·88; difference -1·02, -1·88 to -0·16; p=0·0120). The proportion of patients with at least one adverse event during the double-blind period was slightly higher in patients treated with satralizumab compared with patients treated with placebo (86 [90%] patients vs 67 [73%] patients). Three serious adverse events (in three [3%] patients) were reported in the satralizumab group (pneumonia, pyelonephritis, and increased lipase) compared with nine (in six [7%] patients) serious adverse events in the placebo group (COVID-19, COVID-19 pneumonia, bacterial urinary tract infection, chest pain, back pain, and rosacea). There were no deaths or adverse events of special interest. Satralizumab was well tolerated and resulted in small improvements in patient-reported and clinician-reported outcomes compared with placebo at week 24 in patients with AChR-IgG-positive generalised myasthenia gravis. Further research analysing the immunological underpinnings of the observed clinical response to IL-6 signalling inhibition in patients with generalised myasthenia gravis and exploring the role of IL-6 in autoantibody-mediated diseases is warranted. F Hoffmann La Roche.

Right ventricular stroke work index from echocardiography in patients with pulmonary arterial hypertension, the role in follow-up assessment

Abstract Background Right ventricular (RV) failure cause high mortality in patients with pulmonary arterial hypertension (PAH) (1,2,3,4). RV stroke work index (RVSWI) poses as a possible invasive determinant of outcome. Non-invasively measured RVSWI could be argued useful (5, 6, 7, 8, 9). Echocardiography-derived RVSWI (RVSWIECHO) encompassing either systolic (sPAP) or mean pulmonary arterial pressure (mPAP) is associated with invasive RVSWI (RVSWIRHC). The aim of this study is to evaluate how RVSWI by echocardiography or right heart catheterization (RHC) is altered following PAH-treatment and if RVSWI at baseline is an indicator of outcome in PAH. Methods Fifty-four consecutive patients with PAH (65 ± 13 years, 36 women) analyzed at baseline and at first follow-up visit (141 ± 79 days) were included in the study. Echocardiography and RHC were performed within a median of 0 day [IQR 0-1 days]. PAH-treatment was initiated after baseline examinations. RVSWIRHC was computed as (mPAP-mRAP)xSVIRHC (mRAP: mean right atrial pressure; SVI stroke volume indexed to body surface area). From echocardiography, tricuspid regurgitant (TR) maximum velocity and mean pressure gradient (PG) and SVI were assessed. RVSWIECHO was computed as RVSWIECHO-Max=TRmaxPGxSVIECHO and RVSWIECHO-Mean=TRmeanPGxSVIECHO. Results Invasive sPAP, mPAP and pulmonary vascular resistance (PVR) decreased from baseline to follow-up (sPAP: 76±18 vs 65±20 mmHg; mPAP: 47±11 vs 39±12 mmHg; PVR: 10.3 ±5 to 6.5±3.3 WU; p&amp;lt; 0.01 for all), and SVI increased (29±8 vs 37±10 ml/m2, p&amp;lt;0.01). RVSWIRHC and RVSWIECHOMax-Mean did not differ from baseline to follow-up (RVSWIRHC: 1132±352 vs 1208±467 mmHg*mL*m-2 (p=0.1); RVSWIECHO-Max: 1904±568 vs 1967±727 mmHg*mL*m-2 (p=0.5); RVSWIECHO-Mean: 1090±306 vs 1192±482 mmHg*mL*m-2 (p=0.1)). At long-term follow-up, 40 patients had died. None of the echocardiographic or invasive measures at baseline (including RVSWI) differed between survivors and non-survivors. In univariate Cox proportional hazard analysis, none of the RVSWI methods were associated with long-term mortality. However, age&amp;gt;65 years, six minutes’ walk distance test (6 MWT) &amp;lt;160 m, WHO class III-IV and indexed right atrium volume were associated. Adding these parameters as input in a model of multivariate analysis showed that echocardiography derived RVSWI (RVSWIECHO-Max (HR =1.001; CI 1-1.001; p=0.016); RVSWIECHO-Mean (HR =1.001; CI 1-1.002; p=0.006)) were independently associated with mortality. Conclusion None of the RVSWI methods differed from baseline to follow-up in patients with PAH, despite substantial improvement in conventional hemodynamic parameters. The baseline RVSWI methods were not associated with long-term mortality in univariate analysis. However, when adjusting for clinical variables in a multivariate analysis a significant association between echocardiography-derived RVSWI and mortality could be detected.

Echocardiographic estimate of pulmonary capillary wedge pressure improves outcome prediction in chronic heart failure

Abstract Background An echocardiographic algorithm to estimate pulmonary capillary wedge pressure (ePCWP) and pulmonary vascular resistance (ePVR) has been recently validated versus right heart catheterization (1). Purpose The aim of this study was to assess the prognostic significance of these measures in heart failure (HF) patients. Methods Consecutive outpatients with HF and left ventricular ejection fraction (LVEF) &amp;lt;50% undergoing echocardiography were selected and followed-up for the composite endpoint of cardiac death or HF hospitalization. Results Out of 2,214 patients (71±12 years, 76% males, LVEF 35±9%), ePCWP (16±6 mmHg) was elevated (&amp;gt;15 mmHg) in 52% of cases and ePVR (1.7±0.7 WU) was elevated (&amp;gt;2 WU) in 25% of cases. Patients with increased ePCWP were older, had a higher NYHA class, more pronounced cardiac remodeling, systo/diastolic dysfunction, and neurohormonal activation, particularly when ePVR was also elevated (p&amp;lt;0.001). Over a median follow-up of 33 (17-48) months, both measures stratified patients for the risk of the primary endpoint (Log-Rank 152 for PCWP, and 44 for ePVR, p&amp;lt;0.001). At adjusted regression analysis, ePCWP (hazard ratio for 1 mmHg increase 1.03 [95%CI 1-01-1-05], p&amp;lt;0.001) but not ePVR (p=0.584) predicted the primary endpoint, even in the subpopulation of patients with atrial fibrillation (p=0.003). ePCWP outperformed current diastolic dysfunction grading (Δ C-statistics 0.068 [95% CI 0.045-0.093], p&amp;lt;0.001), and stratified patients’ risk across each diastolic dysfunction grade at univariate analysis (Grade I: p=0.002; Grade II-III: p&amp;lt;0.001; Indeterminate cases: p=0.010). The addition of ePCWP to a multivariable prognostic model, including patients’ age, NYHA class III-IV, chronic obstructive pulmonary disease, estimated glomerular filtration rate, NT-proBNP, and LVEF, improved the accuracy of risk prediction (Δ C-statistics 0.008 [95% CI 0.002-0.014], p=0.007). Conclusion The echocardiographic estimates of PCWP retained clinical and prognostic significance in a large contemporary cohort of patients with chronic HF and LVEF &amp;lt;50%. This algorithm could facilitate early identification of high-risk patients, possibly reducing the need of right heart catheterisation, and allowing a tailored therapeutic approach. Graphical abstract KM curves for the primary endpoint - AF

Combining systemic inflammation biomarkers with traditional prognostic factors to predict surgical site infections in elderly hip fracture patients: a risk factor analysis and dynamic nomogram development

BackgroundSystemic inflammation biomarkers have been widely shown to be associated with infection. This study aimed to construct a nomogram based on systemic inflammation biomarkers and traditional prognostic factors to assess the risk of surgical site infection (SSI) after hip fracture in the elderly.MethodsData were retrospectively collected from patients over 60 with acute hip fractures who underwent surgery and were followed for more than 12 months between June 2017 and June 2022 at a tertiary referral hospital. Biomarkers were calculated from peripheral venous blood collected on admission. The Centers for Disease Control and Prevention (CDC) definition of SSI was applied, with SSI identified through medical and pathogen culture records during hospitalization and routine postoperative telephone follow-ups. Multivariable logistic regression identified independent risk factors for SSI and developed predictive nomograms. Model stability was validated using an external set of patients treated from July 2022 to June 2023.ResultsA total of 1430 patients were included in model development, with 41 cases (2.87%) of superficial SSI and 6 cases (0.42%) of deep SSI. Multivariable analysis identified traditional prognostic factors older age (OR = 1.08, 95% CI 1.04–1.12), ASA class III-IV (OR = 2.46, 95% CI 1.32–4.56), surgical delay ≥ 6 days (OR = 3.59, 95% CI 1.36–9.47), surgical duration > 180 min (OR = 2.72, 95% CI 1.17–6.35), and systemic inflammation biomarkers Platelet-to-lymphocyte ratio (PAR) ≥ 6.6 (OR = 2.25, 95% CI 1.17–4.33) and Systemic Immune-Inflammation Index (SII) ≥ 541.1 (OR = 2.24, 95% CI 1.14–4.40) as independent predictors of SSI. Model’s stability was proved by internal validation, and external validation with 307 patients, and an online dynamic nomogram (https://brooklyn99.shinyapps.io/DynNomapp/) was generated.ConclusionsThis study combined systemic inflammatory biomarkers and developed an online dynamic nomogram to predict SSI in elderly hip fracture patients, which could be used to guide early screening of patients with high risk of SSI and provide a reference tool for perioperative management.

Clinical Characteristics of Primary and Overlap Sjögren's Syndrome-Associated Pulmonary Arterial Hypertension: A Multicenter Retrospective Study.

To explore the clinical characteristics and risk factors for adverse outcomes in patients with Sjögren's Syndrome-associated pulmonary arterial hypertension (SS-PAH). A retrospective analysis was conducted on SS-PAH patients diagnosed by right heart catheterization (RHC) between March 2013 and March 2024 across four Chinese medical centers. Patients were categorized into primary SS-PAH (pSS-PAH) and overlap SS-PAH, based on the presence of additional autoimmune diseases. We compared clinical and demographic data, echocardiographic and hemodynamic parameters, treatment strategies, and event-free survival between the groups. Statistical analyses included t-tests, Wilcoxon rank-sum tests, χ2 tests, Fisher's exact tests, and Kaplan-Meier survival analysis. Overlap SS-PAH was most commonly associated with systemic lupus erythematosus (SLE). Compared with pSS-PAH, overlap SS-PAH patients had a lower proportion of WHO functional class III-IV, lower pulmonary vascular resistance (PVR), and higher cardiac index (CI). They also showed higher treatment success rates and better event-free survival. However, overlap SS-PAH patients with primary biliary cholangitis (PBC) or autoimmune hepatitis (AIH) had significantly lower 1-year event-free survival rates, older age, and elevated alkaline phosphatase (ALP) levels. Overlap SS-PAH generally has a better prognosis than pSS-PAH, with improved exercise capacity and milder hemodynamic abnormalities. However, overlap with PBC/AIH is associated with a poorer prognosis. These findings highlight the heterogeneity of SS-PAH and the need for tailored treatment based on underlying autoimmune conditions. NCT05980728, https://clinicaltrials.gov.

M1 and M2 Macrophage Polarization Correlates with Activity and Chronicity Indices in Lupus Nephritis.

Background: Lupus nephritis (LN) is a severe manifestation of systemic lupus erythematosus (SLE), characterized by inflammation and immune dysregulation in the kidneys. The role of macrophage polarization in LN progression remains underexplored. Objective: This study examined the association between tubulointerstitial M1/M2 macrophage subpopulations and LN indices of activity and chronicity. Materials and Methods: We retrospectively reviewed 160 renal biopsy specimens in patients with LN (ISN/RPS classes II-V) from the database of the Department of Anatomical Pathology, the Faculty of Medicine Vajira Hospital, Navamindradhiraj University (2012-2021). Additional immunohistochemical analysis included CD68, iNOS, CD206, CD163, and evaluation of infiltration with M1 (iNOS+), M2a (CD206+), and M2c macrophages (CD163+). Moreover, clinical information at the time of the renal biopsy, including age, sex, and laboratory findings, was obtained from the electronic medical records. The data were correlated with the macrophage infiltration using the Spearman test. Results: Lupus nephritis biopsies with ISN/RPS class II-V were included (class II: 3 cases (2%), III: 30 cases (19%), III + V: 16 cases (10%), IV: 73 cases (46%), IV + V: 18 cases (11%), and V: 20 cases (12%)). In addition, the mean age of SLE patients at the time of biopsy was 33 years (range: 19-47 years). Most patients were females (n = 141; 88%). The population of CD68+ macrophages was related to serum creatinine (p < 0.001; rs = 0.34). We detected predominantly M2 macrophages across all LN classes, but M1 macrophages demonstrated significant correlations with the activity index (p < 0.001; rs = 0.43). Conversely, M2a and M2c subpopulations were strongly associated with the chronicity index (M2a: p < 0.001, rs = 0.48; M2c: p = 0.024, rs = 0.18). Total macrophages correlated with both indices (activity: p < 0.001, rs = 0.44; chronicity: p < 0.001, rs = 0.42). Conclusions: In lupus nephritis, the predominant population of macrophages is M2. Correlations were noted between the subpopulations of M1 and M2c macrophages and the activity and chronicity indices, respectively. In addition, macrophage populations correlated with disease progression, but the significance of this association in disease progression remains uncertain.

Transcatheter Left Ventricular Reconstruction in HeartFailure Patients With Prior Anterior Myocardial Infarction: The Prospective ALIVE Trial.

Left ventricular (LV) dilatation and extensive scar portend a poor prognosis in heart failure (HF). The Revivent TC system (BioVentrix Inc) is used either during a hybrid transcatheter-surgical or a surgical-only procedure to exclude transmural scar and reduce LV dimensions. The purpose of this study was to examine the safety and efficacy of the Revivent TC® anchor system in patients with HF. We conducted a prospective, multicenter, nonrandomized (2:1 device vs control) trial in patients with NYHA functional class III-IV symptoms, LV ejection fraction≤45%, LV end-systolic volume index≥50mL/m2, and transmural anterior LV scar. Patients with inadequate scar or previous sternotomy served as the control group. The primary safety endpoint was the composite of major adverse events in the device arm compared with a performance goal of 40.5%. The primary effectiveness endpoint was the hierarchical composite of cardiovascular mortality, HF hospitalization, change in 6-minute walk test, change in Minnesota Living With HeartFailure questionnaire score, and change in NYHA functional classification assessed at 12months as the win ratio in the device group compared with the control group. In total, 126 patients (84 device; 42 control) were enrolled at 28 sites. Mean LV ejection fraction was 29.6%±7.2%, and mean LV end-systolic volume index was 93.9 ± 35.5mm. The primary 30-day safety performance goal endpoint was met (major adverse events 15 of 84 [17.9%]; 1-sided 97.5% upper confidence limit 27.7%; P<0.0001). There was no significant difference in the primary 12-month hierarchical composite efficacy endpoint (win ratio 1.13; P = 0.32). In post hoc analysis, the surgical only approach (23 treated patients) had more favorable outcomes than the hybrid approach (60 treated patients). The Revivent TC® system safely reduced LV dimensions in HF patients caused by extensive anterior scar but did not improve clinical effectiveness outcomes at 1 year. A randomized trial is warranted to further define the risks and benefits of the surgical only approach. (BioVentrix Revivent TC™ System Clinical Study; NCT02931240).

Finerenone and new-onset diabetes in heart failure: a prespecified analysis of the FINEARTS-HF trial.

Data on the effect of mineralocorticoid receptor antagonist therapy on HbA1c levels and new-onset diabetes are conflicting. We aimed to examine the effect of oral finerenone, compared with placebo, on incident diabetes in the Finerenone Trial to Investigate Efficacy and Safety Superior to Placebo in Patients with Heart Failure (FINEARTS-HF) trial. In this randomised, double-blind, placebo-controlled trial, 6001 participants with heart failure with New York Heart Association functional class II-IV, left ventricular ejection fraction 40% or higher, evidence of structural heart disease, and elevated N-terminal pro-B-type natriuretic peptide levels were randomly assigned to finerenone or placebo, administered orally. Randomisation was performed with concealed allocation. The primary outcome of the trial was the composite of cardiovascular death and total (first and recurrent) heart failure events (ie, heart failure hospitalisation or urgent heart failure visit). In the present analysis, participants with diabetes at baseline (investigator-reported history of diabetes or baseline HbA1c ≥6·5%) were excluded. New-onset diabetes was defined as a HbA1c measurement of 6·5% or higher on two consecutive follow-up visits or new initiation of glucose-lowering therapy. The full-analysis set comprised all participants randomly assigned to study treatment, analysed according to their treatment assignment irrespective of the treatment received (ie, intention to treat). The safety analysis set comprised participants randomly assigned to study treatment who took at least one dose of the investigational product, analysed according to the treatment actually received. This trial is registered with ClinicalTrials.gov, NCT04435626, and is closed to new participants. Between Sept 14, 2020, and Jan 10, 2023, 6001 participants were recruited and randomly assigned to finerenone or placebo. 3222 (53·7%) participants did not have diabetes at baseline and comprised the study population. During a median duration of follow-up of 31·3 months (IQR 21·5-36·3), 115 (7·2%) participants in the finerenone group and 147 (9·1%) in the placebo group developed new-onset diabetes, corresponding to a rate of 3·0 events per 100 person-years (95% CI 2·5-3·6) in the finerenone group and 3·9 events per 100 person-years (3·3-4·6) in the placebo group. Compared with placebo, finerenone significantly reduced the hazard of new-onset diabetes by 24% (hazard ratio [HR] 0·76 [95% CI 0·59-0·97], p=0·026). Fine-Gray competing risk analysis, accounting for the competing risk of death, yielded a similar finding (subdistribution HR 0·75 [0·59-0·96], p=0·024). Results were similar in sensitivity analyses, in which the definition of new-onset diabetes was expanded to include initiation of SGLT2 inhibitor treatment with diabetes as indication, restricted to HbA1c measurements only, and restricted to new initiation of glucose-lowering drugs only (excluding SGLT2 inhibitor treatment). Findings were similar when participants treated with glucose-lowering drugs at baseline were excluded (n=15). The effect of finerenone, compared with placebo, on new-onset diabetes was consistent across key participant subgroups. Seven participants had an adverse event of new diabetes not captured by any of the definitions above. In participants with heart failure with mildly reduced or preserved ejection fraction without diabetes, oral finerenone reduced the hazard of new-onset diabetes, representing a meaningful additional clinical benefit of this treatment in these individuals. Bayer.

Favorable seizure and developmental outcomes without preoperative intracranial electroencephalography in pediatric patients following epilepsy surgery: A single epilepsy center retrospective study.

At our institute, most pediatric patients undergo epilepsy surgery following a thorough presurgical evaluation without intracranial electroencephalography (EEG). We conducted an initial validation of our noninvasive presurgical strategy by assessing the seizure and developmental outcomes of 135 children. All 135 pediatric patients were <15 years old, had undergone curative surgery, and were followed for at least 2 years postoperatively. Presurgical evaluations and postoperative seizure and developmental outcomes were investigated. Thorough noninvasive evaluation included 3-T magnetic resonance imaging (MRI) and fluorodeoxyglucose positron emission tomography (FDG-PET) in all patients. Intracranial EEG was mainly indicated for patients whose MRIs were negative or subtle. We defined Engel class I as favorable and Engel classes II-IV as unfavorable seizure outcomes. Intelligence quotient (IQ) and developmental quotient (DQ) before and 2 years after surgery were used to assess developmental/neuropsychological outcomes. MRI was positive in 130 of 135 patients (96.3%), including 39 of 40 with focal cortical dysplasia (FCD) type II and 30 of 33 with FCD type I. FDG-PET revealed concordant localizing findings in 119 of 132 patients (90.2%). Ictal single photon emission computed tomography provided concordant localizing information in 85 of 91 patients (93.4%). Intracranial EEG was performed in only 10 of 135 patients (7.4%). Ninety-seven of 135 patients (71.9%) were seizure-free 2 years after surgery. The final seizure-free rate was 99 of 135 (73.3%). Temporal lobe surgery predicted a favorable seizure outcome by multivariate analysis, whereas FCD type I and preoperative IQ/DQ < 70 predicted an unfavorable outcome. The mean IQ change was +1.3 points, and the mean DQ change was +1.0 points. Mean DQ significantly improved following extratemporal surgery (multivariate regression, p < .05), and mean DQ significantly decreased in patients with epileptic spasms (multivariate regression, p < .01). Thorough noninvasive presurgical evaluation enables detection of subtle MRI lesions and curative epilepsy surgery without intracranial EEG in most patients, including those with FCD type II and type I, and leads to favorable seizure and developmental/neuropsychological outcomes.

Predictors of Left Ventricular Ejection Fraction Decrease in Patients With ST-Segment Elevation Myocardial Infarction.

To identify predictors and construct a model for predicting left ventricular (LV) ejection fraction (EF) in patients with ST-segment elevation myocardial infarction (STEMI). This was a prospective registry study of patients with STEMI admitted within the first 24 hours of the disease onset. Patients were evaluated and treated according to the current clinical guidelines. On the first day of STEMI, concentrations of growth stimulating factor, proprotein convertase subtilisin-kexin type 9 (PCSK9), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and high-sensitivity troponin I and C-reactive protein were measured. Echocardiography was performed on the first day and on day 10-12 of admission; LVEF was calculated by the Simpson method. The study included 138 patients; 3 patients were excluded from this part of the study due to death before repeat echocardiography. Based on the LVEF value on day 10-12 of STEMI, the patients were divided into the groups with preserved LVEF (pLVEF) ≥50% (n=34), reduced LVEF (rLVEF) ≤40% (n=21), and moderately reduced LVEF (mrLVEF) 41-49% (n=80). The ordinal regression analysis showed that the factors influencing LVEF in STEMI patients included a history of chronic heart failure, Killip class II-IV acute heart failure at the index hospitalization, the development of LV dilation and postinfarction aneurysm, and an increase in NTproBNP. Based on the obtained estimates of the regression parameters, a prognostic model was constructed that showed the highest sensitivity of the model for predicting rLVEF, 94.4%, mrLVEF, 92.9%, and a lower sensitivity for predicting pLVEF, 62.5%. In the presence of a history of chronic heart failure, Killip class II-IV acute heart failure, developed LV dilation and postinfarction aneurism, and elevated NTproBNP, patients with STEMI are expected to have lower LVEF values.

Long-Term Outcome of Elderly Patients with Severe Aortic Stenosis Undergoing a Tailored Interventional Treatment Using Frailty-Based Management: Beyond the Five-Year Horizon.

Background: Elderly patients with severe aortic stenosis (AS) need individualized decision-making in their management in order to benefit in terms of survival and improvement of quality of life. Frailty, a common condition in elderly patients, needs to be considered when weighing treatment options. Aim: We aimed to evaluate outcomes including survival and functional parameters according to disability criteria at six years of follow-up in an older population treated for severe AS using a frailty-based management. Methods: We evaluated data derived from a pilot clinical project involving elderly patients with severe AS referred to a tailored management based on classification by Fried's score into pre-frail, early frail, and frail and a multidimensional geriatric assessment. A Frailty, Inflammation, Malnutrition, and Sarcopenia (FIMS) score was used to predict the risk of mortality at six years of follow-up. Functional status was evaluated by telephonic interview. Results: At six years of follow-up, we found a survival rate of 40%. It was higher in the pre-frail patients (long rank < 0.001) and in the patients who underwent TAVR treatment (long rank < 0.001). The cut-off FIMS score value of ≥1.28 was an independent determinant associated with a higher risk of mortality at six years of follow-up (HR 2.91; CI 95% 1.7-5.1; p-value 0.001). We found a moderate increase of disability levels, malnutrition status, comorbidities, and number of drugs, but none of them self-reported advanced NYHA class III-IV heart failure. Conclusion: An accurate clinical-instrumental and functional geriatric evaluation in an elderly population with AS is required for a non-futile interventional treatment in terms of survival and functional status even in long-term follow-up.

Transcatheter Aortic Valve Replacement in Aortic Stenosis Patients With New York Heart Association Functional Class III or IV.

Patients with symptomatic aortic stenosis are a vulnerable population with associated cardiac damage and a significant comorbidity burden. In this study we aimed to determine the rate, factors associated with, and prognostic value of poor functional status (New York Heart Association [NYHA] class III-IV) in patients with severe aortic stenosis undergoing transcatheter aortic valve replacement (TAVR). This multicenter study included 6363 transarterial TAVR patients, classified according to baseline functional status (NYHA class I or II vs III or IV). A total of 3800 (60%) patients presented with NYHA class III or IV before the TAVR procedure. Atrial fibrillation (odds ratio [OR], 1.32; 95% confidence interval [CI], 1.11-1.58; P= 0.002), chronic kidney disease (CKD; OR, 1.73; 95% CI, 1.45-2.05; P < 0.001), chronic obstructive pulmonary disease (COPD; OR, 1.65; 95% CI, 1.32-2.05; P < 0.001), reduced left ventricular ejection fraction (OR, 2.28; 95% CI, 1.70-3.05; P < 0.001), and moderate and severe pulmonary hypertension were associated with a poor functional status. At 1-year follow-up, patients with NYHA class III or IV had higher rates of mortality (8.81 per 100 person-years [95% CI, 7.57-10.15] vs 13.12 per 100 person-years [95% CI, 11.80-14.58]; log rank, P < 0.001) and heart failure hospitalization (8.25 per 100 person-years [95% CI, 7.05-9.65] vs 12.5 per 100 person-years [95% CI, 11.24-14.00]; log rank, P= 0.005). Comorbidity factors (COPD, CKD) and signs of cardiac damage (atrial fibrillation, pulmonary hypertension) determined an increased risk of poorer clinical outcomes (P < 0.01 for all). More than half of the patients undergoing TAVR in the contemporary era have presented with advanced functional class before the procedure, and this was associated with a greater comorbidity and cardiac damage burden. Patients with poorer baseline functional status exhibited worse clinical outcomes at 1-year follow-up. These findings highlight the need for further study on earlier interventions for patients with aortic stenosis.

Endothelial progenitor cells have high predictive value for ventricular remodeling after percutaneous coronary intervention in acute myocardial infarction.

Acute myocardial infarction (AMI) and the following heart failure are main causes of disability and death across the globe. Endothelial progenitor cell (EPC) levels are linked to AMI. Herein, we assessed the predictive value of EPCs for post-percutaneous coronary intervention (PCI) ventricular remodeling in AMI patients. This study retrospectively analyzed 215 AMI patients receiving PCI, who were then categorized into the VR (n = 66) and N-VR (n = 149) groups as per whether they developed post-PCI ventricular remodeling. Left ventricular ejection fraction (LVEF), N-terminal pro-brain natriuretic peptide (NT-pro-BNP), and EPCs were measured. The correlations of LVEF and NT-pro-BNP with EPCs, the predictive value of EPCs for post-PCI ventricular remodeling, and the risk of post-PCI ventricular remodeling in AMI patients with different EPC levels were analyzed by Spearman's analysis, receiver-operating characteristic curve, and Kaplan-Meier curve. LVEF and EPC levels were lower and NT-pro-BNP level was higher in the VR group than the N-VR group. EPC levels in the class III-IV group were lower than those in the class I-II group. EPC levels in AMI patients correlated positively with LVEF (r = 0.683) and negatively with NT-pro-BNP (r = -0.761). EPCs exhibited high predictive value for post-PCI ventricular remodeling in AMI [area under the curve (AUC) of 0.822] and anterior MI (AUC = 0.941) patients. AMI and anterior MI patients with low EPC levels had a higher risk of post-PCI ventricular remodeling. Low EPC levels have high predictive value for post-PCI ventricular remodeling, and increase the risk of post-PCI ventricular remodeling in AMI patients.

Survival comparison in adults with congenital systemic to pulmonary shunt and borderline elevated pulmonary vascular resistance versus Eisenmenger syndrome

Pulmonary arterial hypertension (PAH) associated with congenital heart disease (PAH-CHD) is a consequence of unrepaired large systemic-to-pulmonary shunts. The long-term data of adult patients who have PAH-CHD with elevated pulmonary vascular resistance (PVR) are limited. We aimed to investigate the survival of adults who had PAH-CHD with predominantly left-to-right (L-R) shunts with (1) borderline-to-high PVR and (2) treat-and-repair compared with those with Eisenmenger syndrome (ES). From 1995 to 2021, 99 adults with ES (age 34.1 ± 11.2 years) and 118 adults with PAH-CHD with predominantly L-R shunts (age 39.1 ± 13.7 years) were eligible. The PVR in the ES group was 21.0 ± 13.1 WU. Most ES patients (97%) received pulmonary vasodilator therapy. Among the 118 patients with PAH-CHD with predominantly L-R shunts, the baseline PVR was 7.6 ± 4.6 WU, and 78 patients (66.1%) had borderline to high PVR (≥ 5 WU). In the group, 105 patients (88.9%) underwent repair; 84 had defect closure, and 21 had fenestrated closure. Treat-and-repair was used to treat 53 patients with a preoperative final PVR of 3.58 ± 2.63 WU. No early postoperative deaths were reported. At a median follow-up time of 5.4 years (range 0.1–23.6 years), the 10- and 15-year survival rates of adults with borderline PVR were 82.3% and 82.3%, respectively, which were not inferior to the rates for patients with ES, which were 77.8% and 71.2%, respectively (p = 0.41). The survival rate of patients who underwent treat-and-repair was slightly better than that of patients who underwent ES, although the difference was not statistically significant (p = 0.19). Independent mortality risk factors were functional class III-IV at initial presentation (hazard ratio 5.7, 95% CI 1.2–26.6; p = 0.02) and oxygen saturation < 94% at the most recent visit (hazard ratio 9.4, 95% CI 2.1–42.9; p = 0.004).Trial registration: TCTR20200420004.