Citations

Background: The role of body adiposity on metabolic dysregulation in subjects with normal body mass index (BMI) is still under debate with limited population-based evidence. Hypothesis: Body adiposity measured by dual x-ray absorptiometry (DEXA) is associated with metabolic disorders in normal-weight individuals. Methods: We evaluated a sample of adults aged 20-65 who underwent DEXA in the US National Health and Nutrition Examination Surveys from 1999-2006 and 2011-2018. We excluded those with history of cardiovascular disease, cancer, and chronic obstructive pulmonary disease. Weighted logistic regression was performed to test the association between body fat percentage (BF%) and metabolic disorders [e.g., insulin resistance (IR), metabolic syndrome (MS), dyslipidemia, type 2 diabetes mellitus (DM), hypertension]. Models were adjusted for potential confounders while considering complex survey design and were further stratified by sex and BF% as tertiles in normal-weight individuals. IR was tested as a secondary analysis to evaluate the effect on the predicted risk. Results: We included 20,613 individuals (51.5% men, 65.4% non-Hispanic whites), mean age ± SE was 39.42±0.22 years, and 6,424 were normal weight by BMI and represented our study sample. The overall BF% in these subjects measured by DEXA was 28.41±0.19%. In our cohort, metabolic disorders were prevalent in 2.1% to 40.4% of patients (Table 1). Every 10-unit % increase in total BF% was associated with a higher risk for IR, MS, dyslipidemia in the normal weight BMI group (Table 1). Metabolic disorders were associated with BF% tertiles (Figure 1). IR was significantly associated with body fat across all BF% tertiles for men and highest tertiles for women (Figure 2). Conclusion(s): Less than 1/3 of subjects in a representative national sample had a normal BMI. Even in these “normal weight” subjects, increases in body adiposity are significantly associated with increased cardiometabolic disease burden.

Introduction: Biomarkers can facilitate the prediction of events in primary prevention. Few studies have been conducted in the community setting with analyses that incorporate many biomarkers. Hypothesis: We tested whether a multi biomarker model would outperform clinical factors and individual biomarkers for predicting MACE and Stroke/MI in subjects without known CAD. Methods: A retrospective cohort study assessed composite outcomes MACE (MI, CABG, PCI, stroke, and death) and Stroke/MI. Cox proportional hazard models were fit for individual biomarkers, adjusted for age, gender, BMI, hypertension, CAD, and GFR. Multi biomarker models were developed based on AIC values from the single-biomarker models. Bootstrap tests compared survival C-statistics and relative Integrated Discrimination Index (IDI). Results: 1131 patients in Olmsted County, MN were studied. Median age was 63.1 years, 97.5% were Caucasian, and 52.2% were female. Median BMI was 27.8. Kaplan Meier rates of MACE and Stroke/MI were 29.2% (CI = 26.5-31.8%) and 12.3% (CI = 10.3% - 14.3%), at 10 years. Adjusted NT proBNP models showed a 31% increased risk of MACE/death (HR = 1.31; CI = 1.17-1.46) and a 31% increased risk for stroke/MI (HR = 1.31; CI = 1.08-1.58). Adjusted Ceramide score models showed a 13% increased risk of MACE/death (HR = 1.13; CI = 1.04-1.24) and a 29% increased risk for stroke/MI (HR = 1.29; CI = 1.11-1.51). NT proBNP and the Ceramide score with clinical factors was better than clinical factors alone for MACE/Death (Relative IDI = 29.7%; p = 0.003) and Stroke/MI (Relative IDI = 36.1%; p = 0.034). This combined model did not outperform the strongest single biomarker model for Stroke/MI or MACE/Death. Other biomarkers were not significant when added to the combined model. Discussion: Ceramide score and NT proBNP alone and together improve the prediction of MACE and Stroke/MI in a community primary prevention cohort.

Introduction: Intravenous heparin is strongly associated with pocket hematoma (PH) formation in patients undergoing cardiac implantable electronic device (CIED) implantation. However, there is no data on subcutaneous prophylactic heparin in this population Hypothesis: We hypothesized that the subcutaneous heparin may increase the odds of PH in patients undergoing CIED implantation using data from a large, nationally representative sample of the US population. Methods: The Premier Healthcare Database was analyzed from 2016-2019 to identify patients >18 years old undergoing CIED implantation. Patients with PH were then identified by using ICD-10 CM codes. A multivariable logistic regression model was used to adjust for confounders Results: A total of 267,650 patients underwent CIED implantation between January 1, 2016, and December 31, 2019, of which 4,496 (1.68%) \developed PH. Single chamber pacemaker in 7.22%, dual-chamber pacemaker was implanted in 58.3% of patients, and CRT-P in 4.59%, ICD in 18.58%, CRT-D in 11.31%. Of the total cohort, 559 Patients received subcutaneous heparin within 3 days of the CIED implant procedure. Of these 559 patients, 91 (16%) patients were on subcutaneous heparin (pre-procedural: 19; post-procedural: 57) and developed PH. Subcutaneous heparin is associated with increased odds (OR :13.8,p<0.01) of PH formation. Conclusions: This study suggests that subcutaneous heparin is a strong risk factor for the development of PH. This may independently drive up the rates of PH in the inpatient population. Further studies on the timing of subcutaneous heparin need to be conducted.

Introduction: Assessment of right ventricular (RV) size and function by echo is challenging due to complex RV anatomy and requires integration of multiple measurements. We sought to compare accuracy of echo measures of RV size and function with cardiac MRI (CMR) in pulmonary hypertension (PH). Methods: We included patients with PH from the PVDOMICS Study who underwent both echo and CMR. Echo measures of RV size (basal dimension, area, 3D volume) and function (fractional area change [FAC], 3D RV ejection fraction [EF], RV global longitudinal strain [GLS], S’, TAPSE, Tei index) were compared to CMR derived RV volumes and RVEF. Agreement was assessed using Bland-Altman (BA) plots and Lin’s concordance correlation coefficients (ρ c ). Predictive trends were evaluated using linear regression. Results: The cohort included 446 subjects (58 ± 15 yrs, 36% male). Echo measures of RV size showed poor agreement with CMR, but substantial linear associations, when comparing CMR end diastolic volume (EDV) with: echo basal dimension (ρ c = 0.002; β = 60, R 2 = 0.47), end-diastolic area (ρ c = 0.04, β = 6.4, R 2 = 0.64), and 3D EDV (bias = 106, limits of agreement [LOA]: -14.1 to 225); and also when comparing CMR end-systolic volume (ESV) with: end-systolic area (ρ c = 0.08; β = 6.8, R 2 = 0.74) and 3D ESV (bias = 67.3, LOA: -31.8 to 166). Select echo measures of RV function demonstrated better agreement with CMR RVEF including: 3D RVEF (bias -0.23, LOA -17.9 to 17.5) and FAC (ρ c = 0.55; β = 0.89, R 2 = 0.50). Others exhibited modest or poor agreement including: RV GLS (ρ c = 0.11; β = -1.5, R 2 = 0.40), along with S’, TAPSE, and Tei index (ρ c ≤ 0.02; R 2 ≤ 0.19 for all). [Figure] Discussion: In this largest comparison of echo vs CMR measures of RV assessment in PH, echo measures of RV size agreed poorly with CMR, especially at larger RV volumes. RV functional assessment was best with echo 3D RVEF and FAC, which should be preferentially used for echo RV functional assessment. Consider CMR for more accurate volume assessment of RV size.

Introduction: Rilonacept treatment in RHAPSODY resolved active pericarditis recurrences, and long-term treatment led to sustained risk reduction. Prior analysis linked greater baseline Late Gadolinium Enhancement (LGE), with more rapid recurrence upon rilonacept suspension after 12 weeks of treatment. Serial cardiac magnetic resonance (CMR) imaging (T2-STIR, LGE) enabled longitudinal assessment for tracking clinical improvement, guiding decision-making, and predicting patient outcomes after treatment cessation. Methods: At the long-term extension (LTE) 18-month decision milestone (18MDM), investigators chose, based on clinical status, to continue rilonacept, suspend rilonacept/observe, or discontinue the LTE. An imaging core lab blinded to clinical data measured pericardial thickness and graded pericardial edema (T2-STIR) and LGE at baseline and 18MDM. Pericarditis recurrence was assessed clinically following rilonacept suspension. Results: Baseline and 18MDM CMRs were available for 13 patients. Reductions in pericardial thickness, T2-STIR, and LGE from baseline to 18MDM while on treatment are provided in Figure . CMRs were obtained in 7/8 patients suspending rilonacept at 18MDM: LGE was none/trace, and T2-STIR was negative; yet, 5/7 (71%) had pericarditis recurrence within 1-4 months of rilonacept suspension despite prophylactic colchicine (n=2). Conclusions: Continued clinical improvement during prolonged rilonacept treatment corresponded with improvement on CMR, including reduced pericardial thickness, resolution of pericardial edema on T2-STIR, and resolution of LGE. Negative/trace LGE at 18MDM while on treatment did not predict absence of pericarditis recurrence upon subsequent rilonacept suspension in this size-limited subgroup. Larger prospective studies examining CMR parameters in guiding RP treatment duration decisions and informing associated clinical outcomes are warranted.

BACKGROUND Lumbosacral transitional vertebrae (LSTVs) are congenital anomalies that occur in the spinal segments of L5–S1. These vertebrae result from sacralization of the lowermost lumbar segment or lumbarization of the uppermost sacral segment. When the lowest lumbar vertebra fuses or forms a false joint with the sacrum (pseudoarticulation), it can cause pain and manifest clinically as Bertolotti syndrome. OBSERVATIONS A 36-year-old female presented with severe right-sided low-back pain. Computed tomography was unremarkable except for a right-sided Castellvi type IIA LSTV. The pain proved refractory to physical therapy and lumbar epidural spinal injections, but targeted steroid and bupivacaine injection of the pseudoarticulation led to 2 weeks of complete pain relief. She subsequently underwent minimally invasive resection of the pseudoarticulation, with immediate improvement in her low-back pain. The patient continued to be pain free at the 3-year follow-up. LESSONS LSTVs alter the biomechanics of the lumbosacral spine, which can lead to medically refractory mechanical pain requiring surgical intervention. Select patients with Bertolotti syndrome can benefit from operative management, including resection, fusion, or decompression of the pathologic joint.

Abstract Purpose: The neutralizing peptibody trebananib prevents angiopoietin-1 and angiopoietin-2 from binding with Tie2 receptors, inhibiting angiogenesis and proliferation. Trebananib was combined with paclitaxel±trastuzumab in the I-SPY2 breast cancer trial. Patients and Methods: I-SPY2, a phase II neoadjuvant trial, adaptively randomizes patients with high-risk, early-stage breast cancer to one of several experimental therapies or control based on receptor subtypes as defined by hormone receptor (HR) and HER2 status and MammaPrint risk (MP1, MP2). The primary endpoint is pathologic complete response (pCR). A therapy “graduates” if/when it achieves 85% Bayesian probability of success in a phase III trial within a given subtype. Patients received weekly paclitaxel (plus trastuzumab if HER2-positive) without (control) or with weekly intravenous trebananib, followed by doxorubicin/cyclophosphamide and surgery. Pathway-specific biomarkers were assessed for response prediction. Results: There were 134 participants randomized to trebananib and 133 to control. Although trebananib did not graduate in any signature [phase III probabilities: Hazard ratio (HR)-negative (78%), HR-negative/HER2-positive (74%), HR-negative/HER2-negative (77%), and MP2 (79%)], it demonstrated high probability of superior pCR rates over control (92%–99%) among these subtypes. Trebananib improved 3-year event-free survival (HR 0.67), with no significant increase in adverse events. Activation levels of the Tie2 receptor and downstream signaling partners predicted trebananib response in HER2-positive disease; high expression of a CD8 T-cell gene signature predicted response in HR-negative/HER2-negative disease. Conclusions: The angiopoietin (Ang)/Tie2 axis inhibitor trebananib combined with standard neoadjuvant therapy increased estimated pCR rates across HR-negative and MP2 subtypes, with probabilities of superiority &gt;90%. Further study of Ang/Tie2 receptor axis inhibitors in validated, biomarker-predicted sensitive subtypes is warranted.