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Objectives: The performed hand-held echocardiography (HHE) was evaluated and interpreted by trained advanced practice providers (APPs) on hospitalized CHF patients for image quality and interpretation by comparing with expert echocardiographer and SE findings. Background: Congestive heart failure (CHF) is associated with increased hospital admissions and mortality. While a standard echocardiogram (SE) is the gold standard for cardiac assessment, it is not readily available. Hospitalized CHF patients require rapid assessment for expedited treatment. Methods: Over 6 months, five trained APPs performed HHE on hospitalized CHF patients and interpreted: (a) left ventricular (LV) size, (b) LV ejection fraction (LVEF), and (c) right atrial pressure (RAP). The study echocardiographer reviewed and blindly interpreted the HHE images and compared them with APPs and SE findings. Kappa statistics determined the degree of agreement between APPs and the study echocardiographer’s interpretation of the HHE images and SE. Results: A total of 80 CHF patients (age 73 ± 14 years, 58% males; LVEF (by SE) 45 ± 19%; 36.3% body mass indexes ≥ 30 kg/m2) were enrolled. HHE interpretation by APPs had a good agreement for LVEF (kappa 0.79) with the study echocardiographer and SE (kappa 0.74) and a good agreement for RAP (kappa 0.67) with the study echocardiographer. The correlation between the absolute LVEF interpretation by the study echocardiographer on HHE and SE was r = 0.88 (p < 0.0001). Conclusions: Trained APPs obtained diagnostic-quality HHE images and interpreted the LV function and RAP in CHF patients in good agreement with the study echocardiographer. LVEF by HHE correlated with LVEF by SE. Our study suggests trained APPs can use HHE to evaluate LVEF and RAP in CHF patients, leading to expedited and optimized treatment.

AbstractBackgroundThe cardiac and respiratory cycles have been suggested as major drivers of cerebrospinal fluid(CSF) flow. The glymphatic system, one of the mechanisms for the clearance of amyloid‐beta and tau proteins, relies heavily on the movement(flow) of the CSF, and thus, investigating the forces that modulate the CSF flow is essential for understanding the glymphatic flux. Because breathing is trainable through exercise and self‐directed methods, various breathing methods may enhance the CSF flow.MethodReal‐time phase‐contrast MRI(pc‐MRI) was used to measure the CSF flow at the foramen magnum on a 3T. Fast resting‐state fMRI(rsfMRI;TR400ms) was conducted on a compact 3T. Under an IRB‐approved protocol, participants were instructed to breathe slowly and deeply, and subsequently switch to their spontaneous breathing. For rsfMRI data preprocessing, we performed motion correction, skull stripping, spatial smoothing(4mm), temporal filtering(0.01 to 0.1Hz), and linear and quadratic temporal trends removal. fMRI time courses were then normalized to Z‐score at each voxel before being averaged. On the pcMRI, the phase was summed in a CSF region‐of‐interest and plotted vs time. Additionally, we confirmed for possible confounding effects such as head motion or motion‐induced susceptibility changes.ResultrsfMRI findings showed that deep breathing promoted large oscillations in the CSF flow in the ventricles, while spontaneous breathing did not(Figure 1). Additionally, deep breathing resulted in large oscillations in lobar cortical regions. Similar results were observed in the pcMRI, with larger CSF velocity through the foramen magnum during the deep breathing compared to the spontaneous breathing(Figure 2A‐B). The cumulative summation result showed that the volume of CSF flow was increased during deep breathing(Figure 2C).ConclusionThis study provides new evidence that slow and deep breathing promotes CSF flow and global brain BOLD signal, which may be useful in promoting circulation in the brain. The study’s findings also open new avenues for research in the field of neurovascular coupling and mechanisms associated with glymphatic clearance. As hampered CSF flow and/or worsen glymphatic clearance have been shown to associate with pathological aging and dementia, including Alzheimer’s disease and Parkinson’s disease, future research is needed explore the potential of breathing training methods as a non‐pharmacological intervention to support brain health.

Introduction: Lipoprotein (a) [Lp(a)] has been recognized as an independent predictor of atherosclerotic cardiovascular disease (ASCVD). However, there is limited data on the association between Lp(a) levels and risk of recurrent myocardial infarction (MI)/coronary revascularization in patients with acute coronary syndrome (ACS) who underwent percutaneous coronary intervention (PCI). Methods: PubMed/Medline, EMBASE, and Scopus were searched for studies evaluating the association of Lp(a) with recurrent ischemic events from the year 2000-2023. Patients with coronary artery disease or ACS with baseline Lp(a) who underwent PCI or coronary stenting and had outcomes as recurrent MI/ coronary revascularization were included. Random effects models and I 2 statistics were used for pooled hazard ratios (HR), odds ratio (OR), and heterogeneity assessment. A leave-one-out sensitivity analysis was also performed. Results: The initial search resulted in 651 articles, of which nine studies with 27964 patients (mean age 58-66 years, 74.79% male) were included. Of the nine studies, six were retrospective and three prospective. Mean±SD/Median (IQ) follow-up duration was four years [range 2-7 years]. There was an increased risk of recurrent MI/coronary revascularization associated with Lp(a) ≥30 mg/dL (OR, 1.44, 95% CI: 1.09-1.89, I 2 = 79.24%, p=0.009) (Fig 1a) and Lp(a) ≥10-30 mg/dL (OR, 1.19, 95% CI: 1.009-1.416, I 2 = 0%, p=0.039) (Fig 1b), but failed to reach significance with Lp(a) as a continuous variable (OR, 1.004, 95% CI: 0.998-1.009, I 2 = 85.02%, p=0.221) (Fig 1c). Leave-one-out sensitivity analysis showed an equivalent result for various Lp(a) cutoffs (Fig 1a, 1b, and 1c). Conclusions: Our meta-analysis suggests an association of raised Lp(a) with increased risk of recurrent MI/coronary revascularization in ACS patients who underwent PCI.

Purpose: New 2022 European Society of Cardiology/European Respiratory Society PAH guidelines recommend treatment guided by a multi-parameter risk assessment. 1 Patients with low/intermediate risk without cardiopulmonary comorbidities should start dual PAH combination therapy; those with cardiopulmonary comorbidities should be reassessed early for rapid escalation to dual therapy. Initial triple therapy is recommended for high-risk patients. We examined use of dual and triple PAH therapy in the US (before guideline update). Methods: We used the Pulmonary Hypertension Association Registry (PHAR), a prospective US registry of pulmonary hypertension (PH) patients, enrolled within 6 months of their first outpatient visit at one of 54 participating PH care centers in the US, between Sep 2015-Jun 2022. We included adults (≥18 years at enrollment) with incident PAH (newly diagnosed and treated within 6 months of enrollment) and ≥1 follow-up clinic visit post baseline visit. Chronic thromboembolic PH patients were excluded. Results: We analyzed (descriptive statistics) 794 incident patients (baseline characteristics in Table 1). Treatment patterns at baseline (n=794)/last follow-up visit (n=610) were 289 (36.4%)/102 (16.7%) on monotherapy, 419 (52.8%)/314 (51.5%) on dual combination, 83 (10.5%)/179 (29.3%) on triple combination therapy, respectively. Mean time from enrollment to dual and triple combination therapy was 86.1 (standard deviation [SD]: 209.0) and 346.1 days (SD: 430.8), respectively. Conclusions: Among incident PHAR patients, half received initial dual and 10% triple upfront combination therapy. At last follow-up, most (>80%) patients had escalated to dual/triple combination therapies. Clinical Implications: At PH care centers, most incident PHAR patients are escalated to dual and triple therapy (at last follow-up) per current guidelines. Reference 1. Humbert M, et al. Eur Heart J. 2022;43:3618-731.

Introduction: Incident cardiac arrhythmias are common in hospitalized COVID-19 patients, but the impact of a second incident cardiac arrhythmia during hospitalization on clinical outcomes remain unclear. Hypothesis: The aim of this study was to assess the frequency and prognostic implications of a second incident arrhythmia in hospitalized COVID-19 patients over the pandemic course till vaccine availability. Methods: The multicenter COVID-RHYTHM Registry enrolled hospitalized COVID-19 patients from 3/8/2020 to 1/24/2021. Cardiac arrhythmia included documented atrial fibrillation (AF), atrial flutter (AFL), ventricular tachycardia (VT), severe sinus bradycardia (<40 bpm) or AV block. Outcomes were compared between patients with single vs. more than one incident arrhythmias adjusting for baseline variables. Results: Of 6299 hospitalized COVID-19 patients, 4398 had an had an incident cardiac arrhythmia during hospitalization, of which 822 (19%) had a second incident arrhythmia. Those with >1 incident arrhythmia had a higher baseline prevalence of heart failure, chronic kidney disease, coronary artery disease and sleep apnea (Table). Those with >1 incident arrhythmia had higher in-hospital mortality, need for ICU admission and need for rehab upon discharge. Length of stay was similar between the groups. Conclusions: In hospitalized COVID-19 patients with incident cardiac arrhythmias, a second incident arrhythmia during hospitalization was seen in 19%. Having >1 incident arrhythmia was associated with increased need for ICU admission and reduced survival.

Follicular helper T-cell lymphoma of the angioimmunoblastic type (AITL) is associated with dismal prognosis. We performed functional genomic approaches including whole-exome sequencing (WES; n=119), transcriptomic (n=78) and methylation (n=40) analysis. We identified recurrent mutations in known epigenetic drivers ( TET2, DNMT3A, IDH2 R172), and also identified novel ones (TET3, KMT2D). Somatic mutation of all three epigenetic drivers ( TET2, IDH2, and DNMT3A) was associated with poor prognosis (p&lt;.001). Mutations in genes regulating T-cell receptor (TCR) signaling ( CD28 VAV1, FYN, PLCG1) or activation ( RHOA G17V), and regulators of the PI3K pathway (PIK(3)C members, PTEN,PHLPP-1/-2) were also found. Genome-wide DNA-methylation analysis integrated with mRNA expression profiling also revealed epigenetic alterations in genes regulating TCR-RHOA/B/C or PI3K-signaling. TET2 loss was noted in 85% AITLs and was significantly associated with RHOA G17V, CD28 and IDH2 R172mutations. AITLs lacking RHOA G17V tended to have mutations regulating the JAK-STAT pathway ( JAK2, JAK3, STAT1, STAT3, SOCS1). RNA-seq analysis identified fusion transcripts in genes regulating TCR activation (8%), revealed a restricted TCR repertoire in the majority of cases (a=87%, b=72%), and showed the presence of Epstein-Barr virus transcriptome (73%). GEP demonstrated association of B-cells in the tumor-milieu with better prognosis (p=.006), while dendritic cells were associated with worse prognosis (p=.001), which was further validated by immunohistochemistry using CD20, CD68, and CD163 antibodies. RNA-seq and corresponding WES analysis of 12 AITL patient-derived-xenografts (PDX) showed that bi-allelic TET2 mutations, DNMT3A mutations or sub-clonal mutations ( PLCG1 PHLPP2) werepropagated in sequential passages. Gene signatures related to T FH (follicular helper) and T CM (central memory) were also well-maintained in secondary passages in PDX models. Gene signatures of late PDX passages (3 rd-5 th) were enriched with genes related to proliferation and metabolic reprogramming, and in an independent cohort of AITLs, high expression of T3/T5 related signatures was associated with worse outcome (p=0.02/p=0.009). Low mRNA expression of PHLPP2 predicted poor prognosis (p=.03) and engineered PHLPP2 loss showed enhanced PI(3)K activation and FOXO1 inactivation in CD4+ T-cells in-vitro. Thus, we defined the genomic landscape for AITL, which is largely characterized by epigenetic alterations, TCR signaling and PI3K/AKT dysregulation, which may be amenable for therapeutic targeting.