tbuckley/cabot-search huggingface dataset:
Up-Front Treatment of Elderly (Age ≥75 Years) and Frail Patients With Multiple Myeloma
Authors: Nadine Abdallah, Shaji K. Kumar
Journal: Journal of the National Comprehensive Cancer Network (2024)

Older patients with multiple myeloma (MM) exhibit wide heterogeneity in their baseline physiologic and functional status, which demands an individualized treatment approach based on biological rather than chronological age. Various frailty scores have been developed for older patients with MM, but they are underutilized in clinical trials and in practice. Older patients with MM are underrepresented in therapeutic clinical trials, and treatment recommendations are currently derived from clinical trials of transplant-ineligible patients. This article provides a summary of phase II and III clinical trials in transplant-ineligible patients with newly diagnosed MM, highlighting outcomes in patients aged ≥75 years and frailty-based outcomes. The data available thus far show that triplet regimens are more efficacious than doublets in older patients but may be associated with higher toxicity. DRd (daratumumab/lenalidomide/dexamethasone) and VRd (bortezomib/lenalidomide/dexamethasone) are good options in patients who are nonfrail, whereas dose-adjusted DRd and VRd-lite should be offered to frail patients. Frailty should be assessed regularly to guide treatment intensification and/or deescalation. It is important that frailty measures are incorporated in clinical trials evaluating novel treatments to inform how older and frail patients will benefit from these treatments.
Abstract 4135080: Relation of focal and diffuse myocardial fibrosis to left bundle branch block in patients with dilated cardiomyopathy and structurally normal heart
Authors: Elena Rimskaya, Olga Aparina, Olga Stukalova, Semen Kormilitsyn, Nataliia Mironova, Petr Chumachenko, Sergey Ternovoy, Sergey Golitsyn
Journal: Circulation (2024)

The role of fibrosis in etiology of left bundle branch block (LBBB) in still not defined. The aim of this study was to assess the relation of focal and diffuse LV fibrosis to LBBB in patients with dilated cardiomyopathy (DCM) and in patients with structurally normal heart. Materials and methods: 60 DCM with LBBB (DCM-LBBB group, 46.7% male, mean age 57[50;63] years), 50 non-LBBB DCM (78% male, mean age 43[32.3;54] years), 15 patients (53.3% male, mean age 39[28;50] years) with LBBB and no signs of structural heart disease and 10 healthy volunteers (HV) were included in the study. Endomyocardial biopsy (EMB) was performed in 15(24,6%) LBBB-DCM and 16(32%) non-LBBB DCM patients and allowed the quantification of collagen volume fraction (CVF, Fig.1A-D). All patients and HV underwent cardiovascular magnetic resonance (CMR) with late gadolinium enhancement (LGE) analysis. Obtained LGE LV images were post-proceed for core scar (CS) and gray zone (GZ) calculation and 3D reconstruction. Diffuse LV interstitial fibrosis was estimated on all LGE-CMR images with the novel introduced marker - diffuse intensity ratio (DIR). Results: DIR was validated on EMB samples: the percentage of CVF (8.2[4.6;10.8]%) correlated with the DIR value (0.71 ± 0.13) in the same segment (r=0.66, p&lt;0.001, Fig.1E-F). The value of CVF (Fig1A-D) and LGE presence in the septum in both DCM groups (Fig2) was comparable (8.2[4.6; 10.3] versus 7.6[6.1;15.3]%, p=0.82 and 19 (31.7%) versus 17 (34%) patients in non-LBBB DCM group respectively, p=0.8) Moreover, the presence of LGE and midwall fibrosis in septum was not related to the QRS duration (p=0.93 and 0.59). In non-LBBB DCM patients the percentage of CS was significantly higher (4.0[1.55; 11.68]% versus 1.4[0.05;8.5]% in LBBB-DCM patients, p=0.047), whereas percentage of GZ and total fibrosis in both DCM groups was comparable (Fig.3A,B). DIR value was higher in patients with idiopathic LBBB than in HV (0.54±0.09 versus 0.34±0.1, p&lt;0.001) while the percentage of GZ and CS was extremely low and did not differ from its amount in HV (Fig.3C,D). Conclusion: Neither focal (including midwall striae) nor interstitial fibrosis is associated with LBBB in patients with DCM. Diffuse inflammation in LBBB-DCM patients may contribute to the progression of systolic dysfunction but is not the reason for LBBB. The increased value of interstitial fibrosis in patients with LBBB may reflect latent diffuse process in myocardium inexorably leading to DCM development.
Abstract 4134796: Safety of over 1000 consecutive, selected low risk patients with accelerated discharge from a chest pain unit with early generation cardiac troponin use, no cardiac functional or anatomic testing and no clinical risk scores
Authors: Shahad Al Chalaby
Journal: Circulation (2024)

Introduction: Over 6 million patients (pts) present to US emergency departments annually with chest pain (CP), of which the majority are found to have no serious disease. Evaluation of these pts results in substantial costs for unnecessary hospitalization and extensive testing. We evaluated the utility of early discharge of selected low-risk (LR) CP pts from a chest pain unit (CPU) in which no predischarge testing or risk scores were used. Methods: This retrospective study analyzed 1,037 consecutive LR CP pts from a prospectively recorded database. LR was based on normal examination, stable hemodynamics, normal electrocardiograms (ECG), and negative cardiac troponin I, without pre-discharge functional or anatomic cardiac testing or risk scores. We assessed demographics, comorbidities, medications, and major cardiac events at 30 d and 6 mos post-discharge. Results: The study group of 1037 pts comprised 26% of the 4010 pts admitted to the CPU during the study interval from May 2005 to March 2015. Mean patient age was 55 yrs, 56% (n=575) were women, and comorbid conditions were frequent: hypertension (64.1%), dyslipidemia (46.1%), diabetes (25.7%), documented coronary artery disease (19.3%), previous revascularization (20.6%), previous myocardial infarction (10.1%). Length of stay (LOS) in the CPU to discharge was 10.4 hrs. Women received more discharge cardiac medications than men: antiplatelet agents, statins, beta blockers, ACE inhibitors, angiotensin II blockers, calcium channel blockers, and nitrates (p=0.0002 - 0.04). Follow-up (F/U) at 30 d was 91% (n=948) complete and revealed 0.3% (n=3) cardiac deaths, 0.6% (n=6) acute coronary syndromes (ACS), and 6.2% (n= 64) receiving revascularization. F/U at 6 mos was 90% (n=936) complete and total cumulative cardiac deaths were 0.9% (n=9), 0.7% (n=7) ACS and 6.3% (n=65) revascularization. Discussion: Cardiac events at both 30 d and 6 mos were very low and did not differ in men and women (P=0.8). LOS in CPU was minimized and patient safety was maintained. These selected LR pts remained at reduced risk for cardiac events despite a high rate of comorbidities. Early discharge of selected LR CP pts based on history, examination, ECG, and biomarker evaluation was safe and effective. Conclusion: This approach in selected LR pts has the potential to reduce unnecessary diagnostic testing and CPU LOS. This strategy could lead to substantial savings in healthcare costs without compromising patient safety.
Abstract 4135127: Traveling more than a 20-mile radius to a Heart Failure Center can affect the quality of Heart Failure Care.
Authors: Gladys Baksh, Omaima Ali, Michele Haydo, Claudia Mae Velasco, Heather Reesor
Journal: Circulation (2024)

Introduction: We recognized the profound importance of access to care among patients with heart failure (HF). The geographical location of HF centers may significantly impact health outcomes, especially for those with limited transportation. This social determinant of health (SDOH) aspect is critical in bridging the gap in achieving HF care. Hypothesis/Methods: This was a single-center observational study conducted at a tertiary heart failure center in central Pennsylvania. We assessed the impact of travel distance by comparing patients who travel within a 20-mile radius to those who travel beyond a 20-mile radius. A total of 322 patients were referred to the HF clinic and enrolled in a guideline-directed medical therapy (GDMT) optimization program. Data collected included distance to Hershey Medical Center (HMC), health insurance coverage, HF etiology, onset, and echocardiogram. The distance was calculated based on the patient’s zip code. Results: Among patients enrolled in the HF-GDMT program, 194 travel within 20 miles, and 128 travel beyond a 20-mile radius to HMC. The mean travel distance to HMC was 9.1 miles (within) and 40.9 miles beyond 20 miles. The majority of patients were 81.3% white, 67% male, and the average age was 64. Most patients had heart failure with reduced ejection fraction (HFrEF) at 92.9%, 63% nonischemic, and 57.5% new onset. The comorbidities in both groups were similar, including hypertension, hyperlipidemia, and coronary artery disease (CAD). When comparing both groups, those who traveled beyond the 20-mile radius to HMC had more chronic HF at 55.5% vs. 34% in patients who traveled within the 20-mile radius. Upon enrollment, most patients were on suboptimal doses of either 1 or 2 of the four pillars of GDMT for HFrEF. Conclusions: The findings of this study revealed that patients with HF who travel beyond a 20-mile radius to HMC are more likely to have chronic HF, suggesting a delay in seeking care. A delay in referral may affect the timely initiation of appropriate GDMT and will likely lead to worse health outcomes. This underscores the urgent need for interventions to address barriers like transportation to improve HF care, offering a potential avenue for better patient outcomes.
Abstract 4133654: External Validation of the Guha-Stabellini CVD Prostate Cancer-Specific Calculator in Short-Term Follow-Up
Authors: Nickolas Stabellini, Omar Elsayed, Neeraj Agarwal, Jennifer Cullen, Neal Weintraub, Harikrishnan Hyma Kunhiraman, umang swami, Morteza Mahmoudi, John Shanahan, Alberto Montero, Avirup Guha
Journal: Circulation (2024)

Introduction: Conventional cardiovascular disease (CVD) risk scores are inaccurate for prostate cancer patients (PC); the Guha-Stabellini machine learning (GS-ML) score shows promise but lacks external validation. Hypothesis: The GS-ML score is superior to conventional CVD scores in patients with PC. Aim(s): To conduct external validation of the GS-ML score in patients diagnosed with PC. Methods: The validation used holdout data from Seidman Cancer Center’s CAISIS platform (internal validation cohort) and RADICAL PC1 (external validation cohort; a prospective study of men diagnosed with PC within 1 year or starting ADT within 1 month of enrollment), matching covariates with the GS-ML score. With limited follow-up, short-term CVD (2,000 days from PC diagnosis) was the outcome. Performance was assessed via area under the receiver operating characteristic curve (AUC) with assistance from Youden statistic cutoff, comparing metrics with ACC/AHA pooled cohort equations (PCE), SCORE-2, and AHA-PREVENT scores. Atherosclerotic cardiovascular disease (ASCVD) included non-fatal ischemic stroke and myocardial infarction. CVD included ASCVD and heart failure. Results: We included 2,495 patients from RADICAL PC1 and 1,506 from the internal validation cohort ( Table 1 ). In the internal validation cohort, the CVD AUCs were 0.58, 0.49, 0.65, 0,73, and 0.75 for PCE, SCORE2, PREVENT simple, PREVENT enhanced, and GS-ML score, respectively. In RADICAL PC1, the AUCs for CVD were 0.60, 0.43, 0.67, and 0.64 for PCE, SCORE2, PREVENT simple and GS-ML score, respectively. For ASCVD, internal validation cohorts’ AUCs were 0.63, 0.62, 0.66, 0.73, and 0.67 for PCE, SCORE2, PREVENT simple, PREVENT enhanced, and Guha-Stabellini, respectively. The RADICAL PC1 ASCVD AUCs were 0.64, 0.46, 0.65, and 0.61, for PCE, SCORE2, PREVENT simple and GS-ML scores, respectively, Conclusion(s): The GS-ML score was validated for PC patients, showing superior performance to PCE and SCORE2, and similar performance to AHA-PREVENT in predicting CVD. The European Cardio-Oncology guidelines should reconsider using SCORE2 for PC patients. Further improvement and validation with nationally representative datasets are needed to corroborate these findings and enhance the generalizability of the GS-ML score.
Abstract 4137272: The Impact of Genotype in Dilated and Arrhythmogenic Cardiomyopathy: Insights from the SHaRE Registry
Authors: Kishan Padalia, Sarah Slaven, Kristen Medo, Sharon Graw, Brian Claggett, Henning Bundgaard, Adam Helms, Stephane Heymans, Carolyn Ho, Sadiya Khan, Neal Lakdawala, Iacopo Olivotto, Anjali Owens, Sanjay Prasad, Anna Axelsson, Nosheen Reza, Supriya Shore, Gianfranco sinagra, Upasana Tayal, Job Verdonschot, Matthew Wheeler, Matthew Taylor, Marco Merlo, Alessandra Fornaro, Victoria Parikh, Lisa Wilsbacher, Luisa Mestroni
Journal: Circulation (2024)

Background: The impact of genotype on the risk of arrhythmia and heart failure in dilated and arrhythmogenic cardiomyopathy (DCM/ACM) is not well defined. Better understanding of genetic risk factors is needed to improve patient risk stratification, management, and outcomes. Methods: In this observational study, we leveraged the international Sarcomeric Human Cardiomyopathy Registry (SHaRe) to analyze the effect of arrhythmic gene variants on clinical events in patients with DCM/ACM (excluding arrhythmogenic right ventricular cardiomyopathy). Patients were stratified by the presence of pathogenic variants in 8 genes most commonly associated with ACM (AR(+): LMNA , DSP , FLNC , RBM20 , PLN , SCN5A , DES , and TMEM43 ). We assessed for risk of clinical events including ventricular arrhythmia (VA), atrial fibrillation (AF), heart failure (HF), death, and the overall composite of any of these events. Analyses were adjusted for age at diagnosis, sex, and baseline left ventricular ejection fraction (EF). Patients were also stratified by EF ≥50% in subgroup analyses. Results: A total of 1373 genotyped adults with DCM/ACM from 6 centers were included with median follow-up of 5.5 (IQR 2.4-10.4) years. Mean diagnosis age was 48 (± 15) years, and 39.5% were female. The cohort included 185 (13.5%) AR(+) patients. AR(+) compared to genotype-negative patients (N=486, 35.4%) had increased risk of VA (HR 5.02, 95% CI 3.46-7.29) and AF (HR 3.02, 95% CI 2.20-4.10). Risk of HF (HR 2.32, 95% CI 1.55-3.49) and the overall composite (HR 2.12, 95% CI 1.68-2.67) were also increased ( Figure ). Risk of each event remained significant after adjusting for age, sex, and baseline EF ( Table ). AR(+) patients with EF ≥50% also had increased risk of VA (HR 4.56, 95% CI 2.16-9.63), AF (HR 2.94, 95% CI 1.72-5.03), and the overall composite (HR 2.15, 95% CI 1.41-3.28). Conclusions: Genetic testing enables powerful risk stratification for both arrhythmias and heart failure in DCM/ACM independent of age, sex, or EF.
Abstract 4134531: BST2 induces vascular smooth muscle cell plasticity and phenotype switching during cancer progression
Authors: Caitlin Bell, Richard Baylis, Wei Feng Ma, Clint Miller, Nicholas Leeper
Journal: Circulation (2024)

Rationale: Smooth muscle cell (SMC) plasticity and phenotypic switching play prominent roles in the pathogenesis of multiple diseases like atherosclerosis and pulmonary hypertension, but their role in tumorigenesis is unknown. Objective: To investigate SMC diversity and plasticity in tumor angiogenesis and its underlying molecular drivers. Methods and Results: Here we use SMC-specific lineage-tracing mouse models and single cell RNA sequencing (scRNA-seq) to observe the phenotypic diversity of SMCs participating in tumor vascularization. We find that around 10% of SMCs adopt a phenotype which includes features traditionally associated with macrophage-like cells, suggesting they may contribute to the immune profile of the tumor microenvironment (TME). These cells are transcriptionally similar to ‘resolution phase’ M2b macrophages, which have been described to have a role in inflammation resolution. Signaling from bone marrow stromal antigen 2 (BST2) on the surface of tumor cells to PIRA2 on SMC promotes this phenotypic transition, leading to a SMC phenotype that is more proliferative, migratory, and phagocytic. Knockdown of BST2 in the tumor significantly decreases the transition towards a macrophage-like phenotype, and the cells that were able to transition had a comparatively higher inflammatory signal typically associated with anti-tumor effect. Conclusions: As BST2 is known to be a poor prognostic marker in multiple cancers where it is associated with an M2 macrophage-skewed TME, these studies suggest that phenotypically switched SMCs may have a previously unidentified role in this immunosuppressive milieu. The novel concept of SMC contribution to the immune landscape suggests manipulation of SMC phenotypic switching as an approach to altering cancer pathogenesis. Further translational work is needed to understand how this phenotypic switch could influence response to anti-cancer agents and if targeted inhibition of SMC plasticity would be therapeutically beneficial.
Abstract 4134456: Hybrid Cardiac Targeting Peptide Ameliorates HFpEF Phenotype in Mice
Authors: Jack Lopuszynski, Daniella Sahagun, Jingyu Wang, Maliha Zahid
Journal: Circulation (2024)

Introduction: Heart failure with preserved ejection fraction (HFpEF) is a form of heart failure which is rapidly rising in incidence in the US today. Despite this, no therapies with mortality benefit exist for this syndrome. Previous work with our novel hybrid cardiac targeting peptide (hCTP), a cardiomyocyte-specific cell penetrating peptide, has shown multiple beneficial biological effects (improved calcium handling, anti-inflammatory properties) beyond its transduction abilities. Therefore, we hypothesized that treatment with hCTP in a mouse model of HFpEF would ameliorate the pathophysiology of this disease. Methods: To establish a HFpEF model, 6-week-old, C57BL/6NJ mice were placed on a high-fat diet (HFD), 60% kCal from lard, and water with 0.5 g/L of an iNOS inhibitor (N-Nitro-L-arginine methylester) to induce hypertension. After 5 weeks of the diet, HFD mice and their littermate controls underwent baseline exercise testing and echocardiograms. Exercise capacity was measured after 2 days of exercise training with 2 days of rest in between; mice were placed on a treadmill at a 10-degree angle and made to run at increasingly fast speeds (5-30 m/min) until exhaustion. Echocardiograms were performed under 1.5% inhalational isoflurane. After baseline testing, the mice were treated with vehicle, or either 2.5 or 5 mg/Kg hCTP, either 3 or 5 days a week (five groups, n = 3 per group). After four weeks of treatment, the mice were again subjected to the same battery of tests and euthanized. Data was compared using two way ANOVA with Sidak’s test to compare measurements pre- and post-treatment. Results: Treatment with hCTP at either concentration for five days/week led to an increase in running distance from 39.8 m to 116.3 m (p = 0.03, n = 6), compared to changes in control distance from 208.4 m to 157.8 m (p = 0.399). Running distance did not correlate with weight (R 2 &lt; .001). Treatment with 5 mg/Kg hCTP for 5 days/week led to a normalization of the E/e’ ratio, from 43.3 to 26.9 (p = 0.004, n = 3) compared to a change in the control of 34.7 to 26.1 (p = 0.312). Ejection fractions remained consistent (&gt;55%) across all groups. Conclusions: Our data suggests that hCTP appears to be a promising treatment in ameliorating some of the physiological effects in a murine model of HFpEF. Gene and protein expression studies in heart tissue are underway. Further work is warranted with a larger sample size.
Abstract 4134845: Primary Percutaneous Coronary Intervention versus Thrombolytic Therapy Outside Cardiology Reference Center for Acute Myocardial Infarction: A Meta-Analysis of Randomized Control Trials
Authors: Francisco Willamy Alves Filho, Nágila Alves Lima, Vicente Lopes Monte Neto, Wellington Tomaz
Journal: Circulation (2024)

Introduction: Fibrinolysis is the treatment of choice for patients with ST-elevation acute myocardial infarction (STEMI) who cannot reach door-to-balloon time for primary reperfusion therapy (PCI) 1. This therapy is widely used in some countries in Europe and Brazil2. However, these patients who undergo thrombolysis have a higher mortality rate compared to patients who undergo primary PCI3. The objective of the study is to evaluate the outcomes of mortality, reinfarction and stroke in patients with STEMI who underwent thrombolysis outside referral centers (community hospitals and inside ambulances) versus patients who underwent primary PCI. Methods: We performed a systematically review and meta-analysis of randomized control trials (RTCs) comparing of pre-hospital thrombolysis (PHT) with primary coronary intervention (PCI). PubMed, Embase and Cochrane databases were searched from April 2024 with the following search terms: ‘STEMI’, ‘myocardial infarction’[Mesh],’pre hospital’,’thrombolysis’,PHT, ‘thrombolytic therapy’. We used random-effects model to estimate the Risk Ration (RR) with 95% CI. Heterogeneity was examined with I2 statistics. We also performed leave-one-out sensitivity analyses and used Review Manager 5.4 for statistical analysis. The study was registered on PROSPERO: CRD42024547309. Results: A total of 1890 patients from 3 studies RTCs were included. Pre-hospital thrombolysis was used to treat STEMI in 940 patients (49%). Follow-up time varied from 4.6 to 5 years. The average age was 60.3 years. The anterior infarction on the ECG was similar between groups: average 43% (PHT) and 41.6% (PCI). Pre-hospital thrombolysis was associated with a higher risk of reinfarction ( RR 2.33; 95% CI 1.30-4.16; p=0.004; I2=0%) and composite outcomes of stroke, mortality and reinfarction(RR 1.67; 95% CI 1.25-2.23; p=0.0005; I2=0%). No significant differences were found between treatment groups regarding mortality (RR 1.23; 95% CI 0.70-2.18; p=0.47; I2=42%) and stroke (RR 3.82; 95% CI 0.54-27.23; p=0.18; I2=38%). Conclusion: This study suggests that pre-hospital thrombolysis is associated with a higher risk of reinfarction. More randomized studies on patients treated in a pre-hospital environment are needed to better investigate this question.