Serial Changes Research Articles

Serial changes in serum immunoglobulin post kidney transplantation and its viability as a biomarker for infection

Serial changes in serum immunoglobulin post kidney transplantation and its viability as a biomarker for infection

Long-term serial changes in left atrial volume and function after catheter ablation for atrial fibrillation

Abstract Background Catheter ablation for atrial fibrillation (AF) is an effective method to restore and maintain sinus rhythm. The value of left atrial (LA) volume and reservoir function at short-term after ablation have been shown to associate with clinical outcomes. However, data regarding serial changes in LA size and function after the ablation remain scarce. Purpose The purpose of this study was to investigate the serial changes in LA volume and function, and their relationship to the AF recurrence in patients who underwent primary ablation for AF and had preserved left ventricular ejection fraction (LVEF). Methods We retrospectively reviewed 1,204 patients (age: 72±10 years, male: 72%, LVEF: 62±4%, paroxysmal AF: 66%) for whom both pre- and post-procedural serial echocardiographic data were available. Echocardiography was performed at pre-, 1-year, 2-year and 3-year after the ablation procedure. The association between AF recurrence and changes in echocardiographic parameters were evaluated by A repeated measures ANOVA with a Greenhouse-Geisser correction and Bonferroni tests. The AF recurrence was defined as any documented atrial arrhythmia of > 30 seconds after a single ablation procedure. Results During the mean follow-up of 1725±713 days, AF recurrence was observed in 418 patients (34.7%) and persistent AF at last follow-up was 41 patients (3.4%). Patients with AF recurrence had significantly larger LA volume index (LAVI) and lower LA emptying fraction (LAEF) at baseline than those without (50.0±15.5 vs 41.4±14.4 mL/m2, P<0.001, and 31.2±14.9 vs 37.7±14.0 %, P<0.001, respectively) and these differences were maintained thereafter during the follow-up. The trend of LAVI decreased until 6 months later and then remained unchanged regardless of the AF recurrence. These trends were maintained in patients divided into initial paroxysmal and persistent AF. The trend of LAEF increased until 6 months later and then gradually decreased regardless of the AF recurrence. These trends were maintained in patients with persistent AF, however, LAEF continued to decline in patients with paroxysmal AF. (Figure) Conclusions The catheter ablation was associated with significant reduction in LAVI and improvement of LAEF in patients with persistent AF regardless of recurrent AF. In contrast, LAEF decreased gradually in patients with paroxysmal AF. These findings may suggest LA function in patients with AF declines gradually, even when they are maintained in sinus rhythm. However, both LAVI and LAEF in paroxysmal AF were better than persistent AF, suggesting that catheter ablation may be more effective in the paroxysmal AF stage.

Lowering apolipoprotein C-III associates with regression of lipidic plaque materials in type 2 DM patients with coronary artery disease: the pre-specified analysis from the OPTIMAL trial

Abstract Introduction Apolipoprotein CIII (ApoC-III) is a circulating lipoprotein which affects triglyceride-rich lipoprotein metabolism and functionality of high-density lipoproteins. These properties indicate ApoC-III as a potential contributor to atherosclerosis. The OPTIMAL randomized controlled trial (jRCT1052180152) compared the efficacy of continuous glucose monitoring guided versus HbA1c-guided glycemic control on coronary atherosclerosis in Type 2 Diabetes (T2DM) patients by using serial near-infrared spectroscopy/intravascular ultrasound (NIRS/IVUS). Given that NIRS/IVUS imaging enables to quantitatively evaluate plaque burden and its lipidic component in vivo, the OPTIMAL study provides an opportunity to elucidate the association of ApoC-III with change in quantity and quality of coronary plaques. Purpose To elucidate whether serial change in ApoC-III affects the degree of atheroma progression and lipidic plaque materials on NIRS/IVUS imaging. Methods The OPTIMAL trial has serially monitored non-culprit lesions in 94 T2DM patients receiving PCI by NIRS/IVUS imaging. Of these, 46 patients (73 lesions) were included into the current analysis. Circulating ApoC-III levels were measured at both baseline and 48 weeks. The relationships of serial change in ApoC-III with NIRS/IVUS-derived measures [total atheroma volume (TAV) and maximum lipid core burden index in a 4-mm segment (maxLCBI4mm)] were analyzed. Results All of study subjects received a statin, and high-intensity statin was used in 65.2% of them. On-treatment LDL-C and HbA1c levels were 1.9±0.5mmol/L and 7.2±0.7%, respectively. On NIRS/IVUS analysis, any regression of TAV and maxLCBI4mm was observed in 71.2 and 38.4% of analyzed lesions, respectively (Table). There was no significant relationship between change in ApoC-III and TAV regression (r=0.02, p=0.89). However, a reduction of ApoC-III was significantly associated with a greater regression of maxLCBI4mm (r=0.26, p=0.03) (Figure). Furthermore, multivariate analysis adjusting for LDL-C and high-intensity statin use demonstrated lowering ApoC-III level as an independent predictor of maxLCBI4mm regression (OR=0.83, 95%CI=0.69-0.99, p=0.04) (Table). Even in patients receiving high-intensity statin, the relationship of change in ApoC-III with regression of maxLCBI4mm still existed (Figure). Conclusion Serial NIRS/IVUS imaging revealed that a reduction of circulating ApoC-III was associated with a greater regression of maxLCBI4mm. Our findings suggest ApoC-III as an important therapeutic target to modulate lipidic plaque materials in T2DM receiving a statin.Tables

The role of infliximab in treating refractory cardiac sarcoidosis

Abstract Introduction Cardiac sarcoidosis (CS) is associated with therapeutic challenges, and a high morbidity and mortality. Tumour necrosis factor alpha inhibitors like infliximab may be a treatment option for patients with persistent myocardial inflammatory activity despite conventional immunosuppressive treatment with steroids and steroid-sparing agents. Purpose To identify the safety and efficacy of infliximab in the treatment of refractory cardiac sarcoidosis. Methods We conducted a review of refractory CS patients who had been or were actively on treatment with Infliximab at our specialist tertiary care hospital from January 2017 to January 2023. Serial echocardiographic and FDG-PET scan changes as well as long term clinical data on morbidity and mortality was recorded. Results Six CS patients on infliximab were retrospectively identified. The mean age at CS diagnosis was 47.0±5.9 years and mean duration between CS diagnosis and starting infliximab was 21.4±14.2 months (Table 1). Infliximab was commenced due to persistent inflammation on FDG-PET scan and/or CMR despite being on at least two agents (prednisolone and methotrexate ± hydroxychloroquine) in 5 cases and prednisolone alone (intolerance to methotrexate) in one case. At baseline, 3 patients presented with ventricular arrhythmias, 2 with atrioventricular block and 2 with heart failure. After a mean follow up of 21.2±15.5 months of being on infliximab, 5/6 CS patients had decreased myocardial uptake on PET (1 was awaiting a scan) which included complete resolution of FDG-PET signal in one patient (Table 2). A trend in improvement of mean LVEF [52.7±6.6% to 60.2±5.9%, p = 0.10] and reduction of mean prednisolone dose [19.2±6.6mg to 11.3±7.0mg, p = 0.08] was observed during Infliximab treatment. None of the patients had worsening of LVEF or admission with acute heart failure whilst being on infliximab. A total of 4/6 patients had an Implantable Cardioverter Defibrillator device in situ at the time of Infliximab initiation. No major arrhythmias were observed during follow up. One patient died following complications of patent foramen ovale repair. There were three new cases of infection (1 pneumonia and 2 COVID-19 pneumonitis) and one case of renal cell carcinoma diagnosis three years after Infliximab treatment initiation. The drug safety was overall satisfactory since none of the patients required hospitalisation (Table 2). Case 2 patient stopped infliximab after 13 months of treatment and was found to have disease relapse seven months later. During a 20 month follow up of being on infliximab again, he demonstrated complete resolution of FDG uptake on subsequent FDG-PET scan. Conclusion This study supports the use of infliximab in refractory CS by demonstrating improvement in clinical, functional and tissue characterization parameters. However, infliximab is associated with an increased risk of infections.

Elucidating the Heterogeneity of Immunotherapy Response and Immune-Related Toxicities by Longitudinal ctDNA and Immune Cell Compartment Tracking in Lung Cancer.

Although immunotherapy is the mainstay of therapy for advanced non-small cell lung cancer (NSCLC), robust biomarkers of clinical response are lacking. The heterogeneity of clinical responses together with the limited value of radiographic response assessments to timely and accurately predict therapeutic effect-especially in the setting of stable disease-calls for the development of molecularly informed real-time minimally invasive approaches. In addition to capturing tumor regression, liquid biopsies may be informative in capturing immune-related adverse events (irAE). We investigated longitudinal changes in circulating tumor DNA (ctDNA) in patients with metastatic NSCLC who received immunotherapy-based regimens. Using ctDNA targeted error-correction sequencing together with matched sequencing of white blood cells and tumor tissue, we tracked serial changes in cell-free tumor load (cfTL) and determined molecular response. Peripheral T-cell repertoire dynamics were serially assessed and evaluated together with plasma protein expression profiles. Molecular response, defined as complete clearance of cfTL, was significantly associated with progression-free (log-rank P = 0.0003) and overall survival (log-rank P = 0.01) and was particularly informative in capturing differential survival outcomes among patients with radiographically stable disease. For patients who developed irAEs, on-treatment peripheral blood T-cell repertoire reshaping, assessed by significant T-cell receptor (TCR) clonotypic expansions and regressions, was identified on average 5 months prior to clinical diagnosis of an irAE. Molecular responses assist with the interpretation of heterogeneous clinical responses, especially for patients with stable disease. Our complementary assessment of the peripheral tumor and immune compartments provides an approach for monitoring of clinical benefits and irAEs during immunotherapy.

The NICHD Fetal 3D Study: A Pregnancy Cohort Study of Fetal Body Composition and Volumes.

There's a paucity of robust normal fractional limb and organ volume standards from a large and diverse ethnic population. The Fetal 3D Study was designed to develop research and clinical applications for fetal soft tissue and organ volume assessment. The NICHD Fetal Growth Studies (2009-2013) collected 2D and 3D fetal volumes. In the Fetal 3D Study (2015-2019), sonographers performed longitudinal 2D and 3D measurements for specific fetal anatomical structures in research ultrasounds of singletons and dichorionic twins. The primary aim was to establish standards for fetal body composition and organ volumes, overall and by maternal race/ethnicity, and determine whether these standards vary for twins versus singletons. We describe the study design, methods, and details about reviewer training. Basic characteristics of this cohort, with their corresponding distributions of fetal 3D measurements by anatomical structure, are summarized. This investigation is responsive to critical data gaps in understanding serial changes in fetal subcutaneous fat, lean body mass, and organ volume in association with pregnancy complications. In the future, this cohort can answer critical questions regarding the potential influence of maternal characteristics, lifestyle factors, nutrition, and biomarker and chemical data on longitudinal measures of fetal subcutaneous fat, lean body mass, and organ volumes.

Abstract 15357: Assessing the Utility of Serial Fetal Echocardiography in Detecting In-Utero Changes for Single Ventricle Lesions

Introduction: Current guidelines recommend serial fetal echocardiograms (FE) for fetuses with single ventricle lesions (SV) to identify in-utero changes that can impact delivery management, but there is sparse data on the utility of serial FE. We aim to evaluate the incidence of serial FE changes in fetuses with SV. Hypothesis: There is a low incidence of in-utero changes in serial FE for fetuses with SV. Methods: Fetuses with SV and > 1 serial visit between 1/1/2012 to 1/1/2023 were retrospectively reviewed. FE were reviewed for significant, defined serial changes in the following: atrioventricular valve, ventricular function, atrial communication, ductus arteriosus, umbilical artery, umbilical vein, systemic venous Dopplers, hydrops, arrhythmias. Fisher’s exact test was used to compare proportions with change between both segmental findings and SV sub-type. Results: A total of 721 FE for 248 patients were reviewed, the majority with hypoplastic left heart syndrome (HLHS) (64%) and tricuspid atresia (15%). There was a mean of 2.9 visits per patient and 21 days between FE. Out of 3,699 possible changes, there was a total of 56 (1.5%) changes in 41 patients seen on all follow-up FE (Table 1). The most common changes were worsening atrial level restriction (10, 2.4%) and arrhythmias (10, 2.4%), all of which were premature atrial contractions (p<0.01). Out of 56 changes, only 20 (36%) were critical with clinical impact on perinatal management and 2 (4%) showed progressive, serial worsening. Most changes (85%) were noted in the third trimester. There were no differences in incidence of change on serial FE between SV sub-types (p=0.10). Conclusions: SV fetuses have a low incidence of significant physiologic change on serial FE, and progressive worsening of physiologic findings is even rarer. Special consideration should be given to those with HLHS who may develop atrial level restriction. This data should be considered in planning clinical follow-up intervals for fetal SV.

Abstract 13576: Long-Term Serial Changes in Echocardiographic Parameters in Patients With Heart Failure With Preserved Ejection Fraction After Catheter Ablation for Atrial Fibrillation

Background: Heart failure with preserved ejection fraction (HFpEF) is frequently complicated by atrial fibrillation (AF). Catheter ablation for AF is an effective method for restoring and maintaining sinus rhythm (SR). However, there is limited data on the serial changes in echocardiographic parameters in patients with HFpEF after ablation. Hypothesis: The serial changes in echocardiographic parameters after ablation for AF depend not only on baseline rhythm but also on the presence of HFpEF. Methods: A retrospectively review was conducted on 1109 out of 2123 patients who had serial echocardiographic data available before the ablation procedure and at 1-year, 2-year, and 3-year follow-ups. The changes in echocardiographic parameters were assessed using repeated measures ANOVA with a Greenhouse-Geisser correction and Bonferroni tests in four groups, which were divided according to baseline rhythm and HFpEF. HFpEF was defined as an HFA-PEFF score ≥ 5 or 2-4 and left atrial pressure ≥ 15 mmHg at the time of catheter ablation. Results: The prevalence of HFpEF was 51.9%, and paroxysmal AF was present in 65%. Left atrial volume index (LAVI) was larger at baseline in patients with AF and significant decreased after ablation in all groups. The trend of left atrial emptying fraction (LAEF) increased in patients with baseline AF until 1year later, while in patients with baseline SR and HFpEF, LAEF gradually declined even after catheter ablation. The trend of left ventricular ejection fraction increased in patients with baseline AF. The trend of mean E/E’ mildly increased after ablation in all groups. There were significant differences between HFpEF and non-HFpEF. (Figure) Conclusions: Catheter ablation was associated with changes of LA size, function and left ventricular function. Baseline rhythm and the presence of HFpEF play a complex role in the course of cardiac function after ablation.

Serial laboratory biomarkers are associated with ICU outcomes in patients hospitalized with COVID-19.

Clinical utility of routinely measured serial biomarkers in predicting escalation of inpatient care intensity and mortality among hospitalized patients with COVID-19 remains unknown. This retrospective cohort study included patients with COVID-19 who admitted to the Massachusetts General Hospital between March and June 2020 and January to March 2021. White blood cell (WBC) count, platelet count, C-reactive protein (CRP), and D-dimer values were measured on days 1, 3, and 7 of admission. Clinical outcomes include 30- and 60-day morality, ICU transfer, and overall survival (OS) over a follow-up period of 90 days. The association between serial biomarkers and outcomes were assessed using multivariable logistic regression and Cox proportional hazards models. Of the 456 patients hospitalized with COVID-19, 199 (43.6%) were ICU, 179 (39.3%) were medical floor, and 78 (17.1%) were initially admitted to the medical floor and then transferred to the ICU. In adjusted analyses, each unit increase in the slope of CRP was associated with a 42% higher odds of ICU transfer after controlling for the initial admission level (OR = 1.42, 95% CI: 1.25-1.65, P < 0.001). Including serial change in CRP levels from initial level on admission achieved the greatest predictive accuracy for ICU transfer (AUC = 0.72, 95% CI: 0.64-0.79). Serial change in CRP levels from admission is associated with escalations of inpatient care intensity and mortality among hospitalized patients with COVID-19.

Abstract 246: Consumptive Coagulopathy is Associated With Poor Neurological Outcome in Patients With Refractory VT/VF Cardiac Arrest Requiring Extracorporeal Cardiopulmonary Resuscitation

Introduction: Post cardiac arrest syndrome is associated with altered hemostasis. This is aggravated further by the foreign surface in the extracorporeal circuit leading to a coagulofibrinolytic imbalance. Aim: We examined the serial changes of consumptive coagulopathy markers and their association with neurologic outcomes. Methods: A single-center, retrospective cohort study of consecutive patients with VT/VF cardiac arrest meeting criteria for ECMO-facilitated resuscitation (ECPR) between December 2015 and January 2023 were included. Consumptive coagulopathy markers (INR, D-dimer, platelet count, antithrombin III and fibrinogen) were obtained after VA ECMO cannulation and serially on day 1, 2 and 3. We compared the coagulation profiles of patients who had a neurologically favorable outcome (defined as Cerebral Performance Categories (CPC) 1-2) and those with a neurologically unfavorable outcome (CPC 3-5). Results: Of 258 patients, 82 (32%) survived to hospital discharge. Of these, 87% (71/82) survived with favorable neurological outcome. Prolonged INR, elevated D-dimer levels and decreased ATIII levels were associated (p&lt;0.05) with neurologically unfavorable survival and decreased over time (p&lt;0.05)(Figure1). Platelet count and fibrinogen levels were not associated with neurological outcomes. In adjusted analysis (including age, lactate, CPR time and use of dual antiplatelet therapy), each point increase in the INR on day 1, 2 and 3 was associated with neurologically unfavorable survival (OR 4.4, p=0.01; OR 7.14, p=0.04; OR 8.5, p=0.03 respectively). Conclusion: Markers of consumptive coagulopathy with a prolonged INR are associated with unfavorable neurological outcome.

The efficacy of right ventricular pacing for symptomatic left mid-ventricular obstruction.

The serial changes in intraventricular pressure gradient in the left ventricle and NYHA functional classification in each case. Both the left intraventricular pressure gradient and symptoms improved after right ventricular pacing. In one case, the left intraventricular pressure gradient disappeared immediately after right ventricular pacing, while in the others it disappeared during the chronic phase, more than a year later.

Abstract 14884: Variation of Immune Function Assay Within the First Year After Heart Transplantation

Introduction: The ImmuKnow® immune function assay (IFA) is used in heart transplant recipients to measure lymphocyte-mediated cell immunity via CD4 cell ATP production. Values &lt;225 ng/mL are associated with increased infection risk; however, serial changes in the first year after heart transplant are not well reported. We evaluated IFA trends for heart transplant recipients over the first year after transplantation. Methods: This is a single-center cohort study of consecutive heart transplant recipients from 1/1/2014-8/31/2022 that had an IFA obtained within 30-days of transplant and &gt;1 subsequent IFA within the first year after transplant. We described the relative and absolute change of mean IFA in 90-day increments through the first year after transplant, including sex specific differences. Multivariable logistic regression models tested the independent association of patient-level clinical characteristics factors with IFA values &lt;225 ng/mL. Results: In the study cohort, (121/315) (38%) had an IFA within 30-days prior to transplant. Most patients were white non-Hispanic (46%) and male (74%). IFA values decreased from the pre-transplant baseline with mean absolute changes of 92 ng/mL (-24%), 120 ng/mL (-31%), 121 ng/mL (-32%), and 114 ng/mL (-28%) every 90 days after transplant, respectively (panel B). The highest prevalence of an IFA value &lt;225 ng/mL occurred 90-180 days post-transplant in 55/103 (53%) patients. Female patients had a greater absolute and relative decrease in IFA values from baseline and each 90-day period (panel C). In exploratory analysis, at the time of transplant age &gt;60 was associated with a lower risk of IFA values &lt;225 during days 90-180 post-transplant (OR 0.24, p=0.02). A creatinine &gt;1.4 mg/dL was associated with IFA values &lt;225 during 90-180 (OR 3.15, p=0.02) and 180-270 (OR 3.44, p=0.03) days. Conclusion: Heart transplant recipients experienced ~25% reduction in IFA value from baseline in the first-year post-heart transplant.

Radiologic severe osteoarthritis is related to worse clinical outcomes after arthroscopic osteocapsular arthroplasty in primary elbow osteoarthritis for a medium-term follow-up: A retrospective cohort study.

This study aimed to compare the clinical outcomes after arthroscopic OCA in the medium-term follow-up according to the radiologic severity of primary elbow OA and assess serial changes in clinical outcomes in each group. Patients treated using arthroscopic OCA for primary elbow OA with a minimum 3 years of follow-up, from January 2010 to April 2019, were retrospectively assessed for range of motion (ROM), visual analog scale (VAS) pain score, and Mayo Elbow Performance Score (MEPS), preoperatively and at short- (postoperative 3 to 12 months) and medium-term (at least 3 years after surgery) follow-ups postoperatively. Preoperative computed tomography was performed to evaluate the radiologic severity of OA using the Kwak's classification. Clinical outcomes were compared according to the radiologic severity of OA by their absolute values and the number of patients achieving patient acceptable symptomatic state (PASS). Serial changes in the clinical outcomes of each subgroup were also assessed. Of the 43 patients, 14, 18, and 11 were classified as stage I, II, and III groups, respectively; the mean follow-up duration was 71.3 ± 28.9 months and mean age was 56.5 ± 7.2 years. At the medium-term follow-up, stage I group had better ROM arc (I, 114°±14°; II, 100°±23°; and III, 97°±20°; P =.067) and VAS pain score (I, 0.9±1.3; II, 1.8±2.1; and III, 2.4±2.1; P =.168) than stage II and III groups without reaching statistical significance, while stage I group had significantly better MEPS (I, 93.2±7.5; II, 84.7±11.9; III, 78.6±15.2; P = .017) than stage III group. The percentage achieving PASS for ROM arc (P =.684) and VAS pain score (P =.398) were comparable between three groups, however, the percentage achieving PASS for MEPS was significantly higher in the stage I group than stage III group (I vs III, 100.0% vs 54.5%; P =.016). During serial assessment, all clinical outcomes tended to improve at the short-term follow-up. Compared to the short-term period, the ROM arc tended to decrease at the medium-term follow-up while VAS pain score and MEPS overall did not show significant changes. After arthroscopic OCA, stage I showed overall better ROM arc and pain than stage II and III at the medium-term follow-up, while stage I showed significantly better MEPS and higher percentage of patients achieving PASS for MEPS than stage III.

Constitutional and postoperative joint line obliquity can predict serial alignment change after opening-wedge high tibial osteotomy: analysis using coronal plane alignment of the knee classification.

The purposes of this study were (1) to clarify the distribution of the Coronal Plane Alignment of the Knee (CPAK) phenotype in patients who underwent medial opening-wedge high tibial osteotomy (OWHTO) and (2) to identify the predictive factors for postoperative serial alignment changes after OWHTO by analyzing constitutional phenotypes. Patients who underwent OWHTO between March 2014 and December 2019 were retrospectively evaluated. Those who completed a minimum follow-up of 3years were divided into three groups based on the direction of alignment changes from postoperative 3months to the final follow-up: Group 1 (varus direction) when the weight-bearing line ratio (WBLR) change was less than - 4%, Group 2 (maintained) when the WBLR change was between - 4% and 4%, and Group 3 (valgus direction) when the WBLR change was greater than 4%. The following parameters were assessed serially and compared between the groups: (1) radiologic parameters of coronal limb alignment such as joint line obliquity (JLO), (2) CPAK phenotypes, and (3) clinical outcomes. In total, 163 knees were included, and the average duration of follow-up was 4.8 ± 1.6years. More apex distal JLO was observed in the order of Group 1, 2, and 3 at all times (all p < 0.05). The most common CPAK type was type (I + II) (constitutional: apex distal JLO) + type (V + VI) (postoperative 3months: neutral JLO) in Group 1 (29.4%; p = 0.000); otherwise, the most common CPAK type was type (IV + V) (constitutional: neutral JLO) + type (VIII + IX) (postoperative 3months: apex proximal JLO) in Group 3 (11.7%; p = 0.000). Clinical outcomes did not differ between the groups. Constitutional and postoperative JLO were predictive factors of postoperative alignment changes after OWHTO. Constitutional apex distal and postoperative neutral JLO had a tendency for varus alignment progression, whereas constitutional neutral and postoperative apex proximal JLO had a tendency for valgus alignment progression. Retrospective cohort study; Level III.

Serial changes in the coronary artery: isolated immunoglobulin G4-related coronary arteritis.

Serial changes in the coronary artery: isolated immunoglobulin G4-related coronary arteritis.

Longitudinal analysis left ventricular chamber responses under durable LVAD support

Left ventricular assist device (LVAD) support offers remodelling potential in some patients. Our goal was to use non-invasively derived pressure-volume (PV) loops to understand the effect of demographic and device variables on serial changes in cardiac function under pump support. Thirty-two consecutive Medtronic HVAD patients (mean 55.9±12.3 years, 81.3% male) were prospectively recruited. Single-cycle ventricular pressure and volume were estimated using a validated algorithm. PV loops (n=77) and corresponding cardiac chamber dynamics were derived at predefined post-implant timepoints (1, 3, 6 months). Changes in PV loop parameters sustained across the 6-month period were characterised using mixed-effects modelling. The influence of demographic and device variables on the observed changes were assessed. Across a 6-month period, the mean ventricular function parameters remained stable. Significant predictors of monthly improvement of stroke work include: lower pump speeds (2400rpm vs 2500-2800rpm) [0.0.051mmHg/L/month (p=0.001)], high pulsatility index (>1.0 vs <1.0) [0.052mmHg/L/month (p=0.012)], and ischemic cardiomyopathy indication for LVAD implantation (vs non-ischemic) [0.0387mmHg/L/month (p=0.007)]. Various other cardiac chamber function parameters including cardiac power, peak systolic pressure and LV elastance also showed improvements in these cohorts. Factors associated with improvement in ventricular energetics and hemodynamics under LVAD support can be determined with non-invasive PV loops. Understanding the basis of increasing ventricular load to optimise myocardial remodelling may prove valuable in selecting eligible recovery candidates.

Phenotype and fate of liver-resident CD8 T cells during acute and chronic hepacivirus infection.

Immune correlates of hepatitis C virus (HCV) clearance and control remain poorly defined due to the lack of an informative animal model. We recently described acute and chronic rodent HCV-like virus (RHV) infections in lab mice. Here, we developed MHC class I and class II tetramers to characterize the serial changes in RHV-specific CD8 and CD4 T cells during acute and chronic infection in C57BL/6J mice. RHV infection induced rapid expansion of T cells targeting viral structural and nonstructural proteins. After virus clearance, the virus-specific T cells transitioned from effectors to long-lived liver-resident memory T cells (TRM). The effector and memory CD8 and CD4 T cells primarily produced Th1 cytokines, IFN-γ, TNF-α, and IL-2, upon ex vivo antigen stimulation, and their phenotype and transcriptome differed significantly between the liver and spleen. Rapid clearance of RHV reinfection coincided with the proliferation of virus-specific CD8 TRM cells in the liver. Chronic RHV infection was associated with the exhaustion of CD8 T cells (Tex) and the development of severe liver diseases. Interestingly, the virus-specific CD8 Tex cells continued proliferation in the liver despite the persistent high-titer viremia and retained partial antiviral functions, as evident from their ability to degranulate and produce IFN-γ upon ex vivo antigen stimulation. Thus, RHV infection in mice provides a unique model to study the function and fate of liver-resident T cells during acute and chronic hepatotropic infection.

How early can atherosclerosis be detected by coronary CT angiography? Insights from quantitative CT analysis of serial scans in the PARADIGM trial

BackgroundNon-obstructing small coronary plaques may not be well recognized by expert readers during coronary computed tomography angiography (CCTA) evaluation. Recent developments in atherosclerosis imaging quantitative computed tomography (AI-QCT) enabled by machine learning allow for whole-heart coronary phenotyping of atherosclerosis, but its diagnostic role for detection of small plaques on CCTA is unknown. MethodsWe performed AI-QCT in patients who underwent serial CCTA in the multinational PARADIGM study. AI-QCT results were verified by a level III experienced reader, who was blinded to baseline and follow-up status of CCTA. This retrospective analysis aimed to characterize small plaques on baseline CCTA and evaluate their serial changes on follow-up imaging. Small plaques were defined as a total plaque volume <50 ​mm3. ResultsA total of 99 patients with 502 small plaques were included. The median total plaque volume was 6.8 ​mm3 (IQR 3.5–13.9 ​mm3), most of which was non-calcified (median 6.2 ​mm3; 2.9–12.3 ​mm3). The median age at the time of baseline CCTA was 61 years old and 63% were male. The mean interscan period was 3.8 ​± ​1.6 years. On follow-up CCTA, 437 (87%) plaques were present at the same location as small plaques on baseline CCTA; 72% were larger and 15% decreased in volume. The median total plaque volume and non-calcified plaque volume increased to 18.9 ​mm3 (IQR 8.3–45.2 ​mm3) and 13.8 ​mm3 (IQR 5.7–33.4 ​mm3), respectively, among plaques that persisted on follow-up CCTA. Small plaques no longer visualized on follow-up CCTA were significantly more likely to be of lower volume, shorter in length, non-calcified, and more distal in the coronary artery, as compared with plaques that persisted at follow-up. ConclusionIn this retrospective analysis from the PARADIGM study, small plaques (<50 ​mm3) identified by AI-QCT persisted at the same location and were often larger on follow-up CCTA.

Delayed blood pressure recovery after exercise stress test is associated with autonomic dysfunction and pulse pressure in a middle-aged healthy group.

Delayed heart rate (HR) and blood pressure recovery after exercise test is known as the reliable indexes of autonomic dysfunction. Here we tried to evaluate the serial changes in various indicators during exercise test and correlations with recovery of HR and blood pressure in a normotensive healthy middle-aged group. A total of 122 patients without hypertension or diabetes was enrolled (mean age, 55.6 ± 11.0; male, 56.6%; mean blood pressure, 124.8 ± 16.6 / 81.5 ± 9.6 mmHg). Treadmill test was performed for evaluation of chest pain. Patients with coronary artery disease, positive treadmill test result, left ventricular dysfunction or renal failure were excluded. Heart rate recovery was calculated by subtracting the HR in the first or second minute of recovery period from the HR of peak exercise (HRR1 or HRR2). Systolic blood pressure in the 4th minute of recovery stage (SBPR4) was used to show delayed blood pressure recovery. Metabolic equivalents (METs) and HR in stage 2 to 4 were significantly correlated with both HRR1 and HRR2. Multiple regression analysis of HRR revealed significant correlation of METs and SBPR4. SBPR4 was significantly correlated with both HRR1 and HRR2 (HRR1, r = -0.376, p<0.001; HRR2, r = -0.244, p = 0.008) as well as SBP in the baseline to stage 3 and pulse pressure (r = 0.406, p<0.001). Delayed BP recovery after peak exercise test revealed significant association with autonomic dysfunction and increased pulse pressure in normotensive middle-aged healthy group. It can be a simple and useful marker of autonomic dysfunction and arterial stiffness.

Serial Changes in Intestinal Stenotic Stiffness in Patients with Crohn's Disease Treated with Biologics: A Pilot Study Using Ultrasound Shear Wave Elastography.

Intestinal strictures represent an important serious complication of Crohn's disease. Shear wave elastography is a promising noninvasive ultrasound technique for assessing tissue stiffness. This study aimed to evaluate stiffness in the areas of intestinal stricture in patients with Crohn's disease using shear wave elastography and the changes in stiffness after biologics. We enrolled 21 Crohn's disease patients having intestinal stricture. The patients consisted of 3 groups, which were the infliximab naïve (n = 6) group, the ustekinumab naïve (n = 8), and the bio-switch from infliximab to ustekinumab (n = 7) group. Bowell wall thickness was examined by ultrasound sonography, and the stiffness of Crohn's disease stricture lesions was evaluated using Shear wave speed before and 1 year after anti-tumor necrosis factor-alpha antibody infliximab, anti-interleukin 12/23 antibody ustekinumab, and bio-switch from infliximab to ustekinumab. Bowell wall thickness was significantly improved after infliximab, ustekinumab, and the bio-switch. However, shear wave speed indices only in the ustekinumab group significantly decreased after treatment (P = .028), but not in the other group. Shear wave elastography might be a useful method to evaluate stiffness in the areas of intestinal stricture in patients with Crohn's disease treated with biologics. However, a prospective randomized study evaluating the development of obstruction after biological treatment is needed to validate the study findings.