Citations

Backgrounds: Role of coronary artery calcium score (CACS) in acute chest pain patients is currently not well defined. The objective of this study was to investigate the prognostic value of CACS obtained by noncontrast electrocardiogram-gated CT in acute chest pain patients suspected for cardiac origin in emergency department. Methods: We search Pubmed, Embase, Cochrane databases for longitudinal studies of CACS in acute chest pain patients without known coronary artery disease (CAD) in emergency department which reported major adverse cardiovascular events (MACE), consisting of death, nonfatal myocardial infarction (NFMI), revascularization or stroke. Pooled annualized event rate, risk ratios and 95% confidence intervals (CI) were analyzed. A random-effect, generic inverse variance model was used. Result: Eight studies evaluated 3556 patients (mean age = 51 years, 47% men) with the pooled prevalence of hypertension, diabetes mellitus, dyslipidemia and smoking of 42%, 16%, 33% and 33% respectively. During a median follow-up of 5 months (range 1-60 months, 37234 patient-months), the overall pooled MACE rate was 7.6%/y. The pooled event rate of MACE for CACS=0 versus CACS>0 was 0.8%/y (13 events in 18874 patient-months) versus 14.6%/y (224 events in 18360 patient-months). The pooled risk ratio with CACS=0 was 0.04 (95% CI: 0.02-0.07, p<0.001) for MACE compared to CACS>0. The sensitivity, specificity, positive and negative predictive value, positive and negative likelihood ratio of CACS for MACE was 94.5%, 64.1%, 15.8%, 99.4%, 2.63 and 0.09 respectively. The heterogeneity among studies was low with an I 2 of 13%. Conclusion: In acute-chest-pain patients without known CAD presenting to emergency department, MACE was rare in those with CACS=0. Zero CACS by noncontrast electrocardiogram-gated CT in this population has high negative predictive value (>99%) for subsequent cardiac events.

Limb ischaemia is a clinically relevant complication of venoarterial extracorporeal membrane oxygenation (VA ECMO) with femoral artery cannulation. No selective distal perfusion or other advanced techniques were used in the past to maintain adequate distal limb perfusion. A more recent trend is the shift from the reactive or emergency management to the pro-active or prophylactic placement of a distal perfusion cannula to avoid or reduce limb ischaemia-related complications. Multiple alternative cannulation techniques to the distal perfusion cannula have been developed to maintain distal limb perfusion, including end-to-side grafting, external or endovascular femoro-femoral bypass, retrograde limb perfusion (e.g., via the posterior tibial, dorsalis pedis or anterior tibial artery), and, more recently, use of a bidirectional cannula. Venous congestion has also been recognized as a potential contributing factor to limb ischaemia development and specific techniques have been described with facilitated venous drainage or bilateral cannulation being the most recent, to reduce or avoid venous stasis as a contributor to impaired limb perfusion. Advances in monitoring techniques, such as near-infrared spectroscopy and duplex ultrasound analysis, have been applied to improve decision-making regarding both the monitoring and management of limb ischaemia. This narrative review describes the evolution of techniques used for distal limb perfusion during peripheral VA ECMO.

AbstractIntroductionVentricular tachycardia storm or electrical storm (ES) is a common complication following left ventricular assist device (LVAD) implantation. The factors contributing to ES and outcomes are less studied. The study aimed to determine the factors associated with ES and the probability of survival in patients undergoing LVAD in three tertiary centers over a span of 15 years.MethodsWe performed a retrospective cohort study on all patients who underwent LVAD implantation at the Mayo Clinic (Rochester, Phoenix, and Jacksonville) from January 1, 2006 to December 31, 2020. ES was defined as ≥3 episodes of sustained ventricular tachycardia over a period of 24 h with no identifiable reversible cause. Detailed chart reviews of the electronic health records within the Mayo Clinic and outside medical records were performed.ResultsA total of 883 patients who underwent LVAD implantation were included in our study. ES occurred in 7% (n = 61) of patients with a median of 13 days (interquartile range [IQR]: 5–297 days) following surgery. We found 57% of patients (n = 35) developed ES within 30 days, while 43% (n = 26) patients developed ES at a median of 545 (IQR 152–1032) days after surgery. Following ES, 26% of patients died within 1 year. Patients with ES had a significant association with a history of ventricular arrhythmias and implantable cardioverter defibrillator (ICD) shocks before the procedure. ES was significantly associated with reduced survival compared to patients without ES (hazards ratio [HR]: 1.92, 95% CI: 1.39–2.64, p < .001).ConclusionFollowing LVAD implantation, the rate of ES was 7% with majority of ES occurring within 30 days of LVAD. Risk factors for ES included pre‐implant history of ventricular arrhythmias and ICD shock. ES was significantly associated with reduced survival compared to patients without ES.

Background Percutaneous heart valve procedures have been increasingly performed over the past decade, yet real‐world mortality data on valvular heart disease (VHD) in the United States remain limited. Methods and Results We queried the Centers for Disease Control and Prevention's Wide‐Ranging Online Data for Epidemiologic Research database among patients ≥15 years old from 1999 to 2020. VHD and its subtypes were listed as the underlying cause of death. We calculated age‐adjusted mortality rate (AAMR) per 100 000 individuals and determined overall trends by estimating the average annual percent change using the Joinpoint regression program. Subgroup analyses were performed based on demographic and geographic factors. In the 22‐year study, there were 446 096 VHD deaths, accounting for 0.80% of all‐cause mortality (56 014 102 people) and 2.38% of the total cardiovascular mortality (18 759 451 people). Aortic stenosis recorded the highest mortality of VHD‐related death in both male (109 529, 61.74%) and female (166 930, 62.13%) populations. The AAMR of VHD has declined from 8.4 (95% CI, 8.2–8.5) to 6.6 (95% CI, 6.5–6.7) per 100 000 population. Similar decreasing AAMR trends were also seen for the VHD subtypes. Men recorded higher AAMR for aortic stenosis and aortic regurgitation, whereas women had higher AAMR for mitral stenosis and mitral regurgitation. Mitral regurgitation had the highest change in average annual percent change in AAMR. Conclusions The mortality rate of VHD among the US population has declined over the past 2 decades. This highlights the likely efficacy of increasing surveillance and advancement in the management of VHD, resulting in improved outcomes.

Abstract Background: R/R FL is an incurable disease and outcomes worsen with successive relapses. A high unmet need remains for therapies that improve tumor control and extend survival after relapse. Odronextamab, an off-the-shelf CD20×CD3 bispecific antibody, demonstrated compelling efficacy, generally manageable safety, and maintenance of pt-reported overall quality of life scores from baseline in an interim analysis of the ELM-2 study (NCT03888105) in heavily pretreated pts with R/R FL (Villasboas et al. ASH 2023). Here, for the first time, we present the primary analysis of R/R FL in ELM-2. Methods: IV odronextamab was administered in 21-day cycles (C) until disease progression/unacceptable toxicity. Steroid prophylaxis and step-up dosing (0.7/4/20 mg) were used in C1 to mitigate the risk of cytokine release syndrome (CRS), followed by 80 mg on Days (D) 1, 8, and 15 of C2-4. Maintenance dosing continued at 160 mg Q2W, or Q4W if complete response (CR) was durable for 9 months (mo). Primary endpoint was objective response rate (ORR) per Lugano criteria by independent central review (ICR). Secondary endpoints included CR rate, duration of response (DOR), progression-free survival (PFS), and overall survival (OS). Primary analysis was performed when 128 pts had ≥52 weeks’ follow-up. Results: At data cutoff (Oct 20, 2023), 128 pts with FL Grade (Gr) 1-3a were evaluable for efficacy and safety: median age 61 yrs (range 22-84); FLIPI risk score 3-5 57.8%; POD24 49.2%; median 3 prior lines of therapy (2-13); 71.9% refractory to last treatment (Tx); 74.2% refractory to an anti-CD20 antibody. The median no. of Tx cycles was 19.4 (0.1-95.9); 95.3% and 85.2% of pts completed C1 and C4, respectively.Median efficacy follow-up was 20.1 mo; ORR was 80.5% and CR rate was 73.4% confirmed by ICR. Responses were durable (median DOR 22.6 mo; median DOCR 25.1 mo). Median PFS was 20.7 mo and 24-mo PFS was 46.1%. Median OS was not reached and 24-mo OS was 70.1%.The odronextamab safety profile was generally manageable and consistent with previous reports. Tx-emergent adverse events (AEs) occurred in all pts (Gr ≥3 85.9%); 15.6% had AEs leading to Tx discontinuation. With 0.7/4/20 mg step up (n=60), CRS events were mostly low grade (Gr 1 45.0%; Gr 2 10.0%; Gr 3 in 1 pt), occurred mostly in C1, and resolved in a median of 2 days; ICANS was reported in 1 pt (Gr 2). Infection rates were consistent with heavily pretreated, immunosuppressed pts (Leonard et al. JCO 2019; Hayne et al. BBMT 2020), occurring in 79.7% (102/128) of pts (Gr 4/5 14.0%; COVID-19 36.7% [Gr 5 6.3%]).Conclusion: Odronextamab demonstrated deep and durable responses in heavily pretreated pts with R/R FL; 91% of responders achieved CR, correlating with favorable PFS and OS at 24 mo. Odronextamab had a generally manageable safety profile and a low incidence of Gr 3 CRS/ICANS. Odronextamab could offer an important off-the-shelf Tx option for pts with heavily pretreated R/R FL. Citation Format: Geoffrey Chong, Michal Taszner, Silvana Novelli, Seok-Goo Cho, Jose C. Villasboas, Ana Jiménez Ubieto, Benoît Tessoulin, Michelle Poon, David Tucker, Jan Walewski, Yuqin Song, Emmanuel Bachy, Stephanie Guidez, Aranzazu Alonso, Deepa Jagadeesh, Stefano Luminari, Laura Magnano Mayer, Elżbieta Iskierka-Jażdżewska, Monica Tani, Jingxian Cai, Amulya Uppala, Saleem Shariff, Jurriaan Brouwer-Visser, Aafia Chaudhry, Hesham Mohamed, Srikanth Ambati, Tae Min Kim. Primary analysis of the Phase 2 ELM-2 study: Odronextamab in patients (pts) with relapsed/refractory follicular lymphoma (R/R FL) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT243.