High Events Research Articles

Abstract 13238: Persistence of High Rates of Major Adverse Cardiovascular Events at 1 Year Post-Myocardial Infarction in Patients With Multivessel Disease: A Systematic Literature Review

Background: Multivessel disease (MVD) heightens the risk of major adverse cardiovascular events (MACE) in post-myocardial infarction (MI) patients. The risk of MACE is elevated in the early period after an MI, a period unaddressed by current secondary preventative therapies. Research aims: To better understand the impact of MVD on clinical and patient-centered outcomes post-MI in the current treatment landscape. Methods: A systematic literature review was conducted to identify relevant articles published between March 2019 and July 2022 from MEDLINE, Embase, Cochrane databases, and cardiovascular (CV) and health outcomes conferences. Articles reporting on pre-specified clinical or patient-centered outcomes in post-MI patients with MVD at timepoints within 1 year were included. Studies that included patients with cardiogenic shock were excluded from this review. Results: Clinical and patient-centered outcomes were reported in five randomized-controlled trials (RCTs) and 24 observational studies across 30 articles; and one RCT across two articles, respectively. Although the definition of MVD varied, it was generally characterized by ≥50% stenosis in ≥1 noninfarct-related coronary artery. Rates of individual MACE endpoints (all-cause mortality, CV mortality, MI, stroke) were variable (Table), likely due to heterogeneity in study populations and interventions. Nevertheless, a key trend was identified; MACE rates at 1-year post-MI were typically not substantially higher than those at earlier timepoints. EQ-5D scores, reflective of quality of life (QoL), increased following treatment; however, increases were marginal, indicating minimal improvements in QoL. Conclusions: MVD is associated with high rates of MACE early after MI that persist at 1 year. Novel therapies that address CV risk in the early period post-MI may support improved CV outcomes among patients with MVD. Further data on patient-centered outcomes are warranted.

Characterization of cardiac arrhythmias and maternal–fetal outcomes in pregnant women: A prospective cohort study

Introduction and ObjectivesCardiovascular disease is a common cause of morbidity and mortality in pregnant women. Arrhythmias are common complications during pregnancy; however, the data are limited. Our goal was to characterize the epidemiology, clinical presentation, and impact of cardiac arrhythmias on maternal–fetal outcomes. MethodsA prospective cohort study from the Colombian Registry of Pregnancy and Cardiovascular Disease was carried out from 2016 to 2019. All patients with tachyarrhythmia or bradyarrhythmia and a minimum follow-up of six months after delivery were included. The primary outcome was a composite of cardiac events defined as pulmonary edema, symptomatic sustained arrhythmia requiring specific therapy, stroke, cardiac arrest, or maternal death. Secondary outcomes were other cardiac, neonatal, and obstetric events. ResultsArrhythmias were the most common cause of referral to our dedicated cardio-obstetric clinic. A total of 92 patients were included, mean age 27±6 years; 8.7% had previous structural heart disease, and cardiology consultation was delayed in 79.4%. The most common arrhythmias were premature ventricular contractions (33%) and paroxysmal reentrant supraventricular tachycardias (15%); 11 patients (12%) had cardiac implantable electronic devices. Cardiac events occurred in 18.4% of patients, obstetric events occurred in 6.5%, and one caesarean was indicated in the context of symptomatic severe mitral stenosis. Adverse neonatal outcomes were observed in 24.3% of newborns. ConclusionsArrhythmias were the most common cause of referral to a dedicated cardio-obstetric clinic; most had a benign course. Adverse maternal cardiovascular outcomes were significant and there was a high rate of obstetric and neonatal adverse events, underlining the importance of multidisciplinary care.

High Rates of Thrombotic Events in Newly Diagnosed Multiple Myeloma Patients Enrolled on the Maia Trial

Background. Patients with newly diagnosed multiple myeloma (NDMM) have a nine-fold increased risk of developing venous thromboembolism (VTE). Despite the availability of the IMWG and NCCN VTE prophylaxis guidelines and updated risk stratification models such as SAVED and IMPEDE, the optimal thromboprophylaxis strategy is unknown, especially in the age of modern daratumumab-containing regimens. To continue highlighting the importance of appropriate thromboprophylaxis for patients with NDMM, we performed a post-hoc analysis of the randomized phase 3 MAIA trial to identify rates of venous and arterial thromboembolism. Methods. This retrospective study, carried out under YODA Project #2021-4663, used data from the randomized phase 3 MAIA trial that investigated lenalidomide and dexamethasone (Rd) with or without daratumumab (DRd) in 733 transplant ineligible (TIE) patients obtained from the Yale University Open Data Access (YODA) Project, which has an agreement with JANSSEN RESEARCH & DEVELOPMENT, L.L.C.. Thrombotic events (TE), including both venous and arterial events (V/ATE) were examined with VTE events including deep vein thrombosis (DVT), pulmonary embolism (PE), and superficial thrombophlebitis (SVT). Arterial events (ATE) included cerebrovascular accidents (CVA) defined as hemorrhagic, ischemic, or verebrobasilar strokes. The incidence and time to event of V/ATE were calculated and graded using the CTCAE v4, with Grade 1 representing nonactionable venous thrombosis, Grades 2-4 representing TEs requiring increasing higher levels of medical intervention, and Grade 5 indicating death was a result of the TE. Rates and time to events were compared between the DRd and Rd arms. Results. Of the included patients, median age was 72 years (range 64-72) and 48% were female. There was no signficant difference between baseline characteristics of sex, race, myeloma subtype, presence of high-risk cytogenetics, or ISS staging between patients that experienced a V/ATE event and those that did not. All grade V/ATE events were 18% (66/363) and 19% (70/365) in the DRd and Rd arms, respectively. Of these, most were VTE events in both arms (16%), with G2-4 actionable VTE event rate of 14.9% vs 14.8% for the DRd and Rd arms, respectively. G5 VTE events were 0.2% in both arms (no G5 ATEs). ATE were 2.2% and 2.7% in the DRd and Rd group, respectively, overall constituting a minority of events. The overall PE rate was higher in the DRd than Rd arm, 6.3% vs 4.7%, DVT was more frequent in the Rd arm, 9.6% vs 7.7%, and rates of SVT rates were similar between both arms at 1.9% and 2.2% for the DRd vs Rd arms, respectively (Table 1). Median time to onset of cumulative TEs was longer in DRd vs Rd arm, 7.15 (0.27 - 63.0) vs 4.65 (0.03 - 58.0) months, respectively. Among these, median time to onset of VTE was similar among the groups [6.57 (0.27 - 63.0) vs 4.48 (0.03 - 52.9) months, respectively] while the median time to onset of ATEs was longer in DRd vs Rd arm, 19.8 (1.70 - 26.6) vs 8.3 (0.67 - 58.5) months. The incidence of VTE events persisted past 24 months and incidence of ATE events increased over time (Figure 1). Analysis regarding prophylactic anticoagulation use and rates of TE based on prophylactic regimen are ongoing. Conclusion. This retrospective study reveals the highest reported rates of VTE in any modern therapy dataset. In patients with transplant ineligible NDMM, we show that the TE risk persists past 24 months of treatment in patients on DRd or Rd therapy. Similar to observations in the GRIFFIN trial, the addition of daratumumab did not increase the risk of TE. Our report highlights the critical need for further investigation of optimal prophylactic strategies and their duration for patients with NDMM.

Experimental certification of more than one bit of quantum randomness in the two inputs and two outputs scenario

One of the striking properties of quantum mechanics is the occurrence of the Bell-type non-locality. They are a fundamental feature of the theory that allows two parties that share an entangled quantum system to observe correlations stronger than possible in classical physics. In addition to their theoretical significance, non-local correlations have practical applications, such as device-independent randomness generation, providing private unpredictable numbers even when they are obtained using devices delivered by an untrusted vendor. Thus, determining the quantity of certifiable randomness that can be produced using a specific set of non-local correlations is of significant interest. In this paper, we present an experimental realization of recent Bell-type operators designed to provide private random numbers that are secure against adversaries with quantum resources. We use semi-definite programming to provide lower bounds on the generated randomness in terms of both min-entropy and von Neumann entropy in a device-independent scenario. We compare experimental setups providing Bell violations close to the Tsirelson’s bound with lower rates of events, with setups having slightly worse levels of violation but higher event rates. Our results demonstrate the first experiment that certifies close to two bits of randomness from binary measurements of two parties. Apart from single-round certification, we provide an analysis of finite-key protocol for quantum randomness expansion using the Entropy Accumulation theorem and show its advantages compared to existing solutions.

The Role of Luminal Apposing Metal Stents on the Treatment of Malignant and Benign Gastric Outlet Obstruction.

Gastric outlet obstruction (GOO) is a clinical syndrome traditionally managed by surgical gastrojejunostomy or enteral stenting. The surgical approach is burdened with a high rate of adverse events (AEs), while enteral stenting has a limited long-term clinical effectiveness, with the need for repeat procedures. The availability of lumen-apposing metal stents (LAMSs) has resulted a shift in the treatment paradigm of GOO. Indeed, endoscopists are now able to create a stable anastomosis between the stomach and small bowel under endosonographic guidance. EUS-guided gastro-enteroanastomosis (EUS-GE) has the theoretical advantage of a durable luminal patency resulting from stent placement away from the site of obstruction, free from surgical-related AEs. This approach could be especially valuable in terminally ill patients with a limited life expectancy. The present paper reviews procedural techniques and clinical outcomes of EUS-GE in the context of both malignant and benign GOOs.

Effects of complete revascularization according to age in patients with ST-segment elevation myocardial infarction and multivessel disease (COMPLETE-AGE)

BackgroundIn ST-segment elevation myocardial infarction (STEMI), complete revascularization with percutaneous coronary intervention (PCI) reduces major cardiovascular events compared with culprit-lesion-only PCI. Whether age influences these results remains unknown. MethodsCOMPLETE was a multinational, randomized trial evaluating a strategy of staged complete revascularization, consisting of angiography-guided PCI of all suitable non-culprit lesions, versus a strategy of culprit-lesion-only PCI. In this pre-specified subgroup analysis, treatment effect according to age (≥65 years versus <65 years) was determined for the first co-primary outcome of cardiovascular (CV) death or new myocardial infarction (MI) and the second co-primary outcome of CV death, new MI, or ischemia-driven revascularization (IDR). Median follow-up was 35.8 months (interquartile range [IQR]: 27.6 to 44.3 months). ResultsOf 4,041 patients randomized in COMPLETE, 1,613 were aged ≥ 65 years (39.9%). Higher event rates were observed for both co-primary outcomes in patients aged ≥ 65 years comparted with those aged < 65 years (11.2% vs. 7.9%, HR 1.49, 95% CI 1.22-1.83; 14.4% vs. 11.8%, HR 1.28, 95% CI 1.07-1.52, respectively). Complete revascularization reduced the first co-primary outcome in patients ≥ 65 years (9.7% vs 12.5%, HR 0.77; 95% CI 0.58-1.04) and < 65 years (6.7% vs 9.1%, HR 0.72; 95% CI 0.54-0.96)(interaction P=0.74). The second co-primary outcome was reduced in those ≥ 65 years (HR 0.56, 95% CI 0.43-0.74) and < 65 years (HR 0.48, 95% CI 0.37-0.61 (interaction P=0.37). A sensitivity analysis was performed with consistent results demonstrated using a 75-year threshold (albeit attenuated). ConclusionsIn patients with STEMI and multivessel CAD, complete revascularization compared with culprit-lesion-only PCI reduced major cardiovascular events regardless of patient age and could be considered as a revascularization strategy in older adults.

Carotid Endarterectomy With Simultaneous Proximal Common Carotid Endovascular Intervention is Beneficial for Symptomatic Stenosis and Likely Confers No Advantage for Asymptomatic Lesions.

Carotid bifurcation stenosis may co-exist simultaneously with more proximal common carotid artery (CCA) atherosclerotic plaquing, primarily at the vessel origin in the aortic arch. This scenario is relatively infrequent and its' management does not have quality randomized data to support medical vs surgical treatment. It is logical to treat any high grade common carotid lesions proximal to a carotid bifurcation endarterectomy (CEA) site both to prevent perioperative emboli or thrombosis as well as future embolization. Prior long-term investigations of the combined treatment paradigm have been low volume analysis. Further, prior studies focus on perioperative outcomes with respect to stroke prevention. The only prior VQI study investigating mid-term outcomes following simultaneous CEA with proximal CCA endovascular therapy provided data on less than 10 patients beyond 1.5years. The long-term follow-up (LFTU) component initiative within VQI has been emphasized in recent years, now allowing for much more robust LTFU analysis. Four cohorts were created for perioperative outcome analysis and Kaplan Meier freedom from event analysis: CEA in isolation for asymptomatic disease; CEA in isolation for symptomatic patients; CEA with proximal CCA endovascular intervention for asymptomatic; and, CEA with proximal CCA intervention for symptomatic patients. Binary logistic multivariable regression was performed for perioperative neurological event and 90-day mortality risk determination and Cox multivariable regression analysis was performed for long term freedom from cumulative ischemic neurological event and long-term mortality analysis. Symptomatology and type of surgery (CEA with or without CCA intervention) were individual variables in the multivariable analysis. Neurological ischemic event in this study encompassed transient ischemic attack (TIA) and stroke combined. We noted a statistically significant (P < .001) escalation in rates of perioperative neurological event, myocardial infarction (MI), carotid re-exploration, 90day mortality and combined neurological event and 90day mortality moving from: A) asymptomatic CEA in isolation to B) symptomatic CEA in isolation to C) asymptomatic CEA combined with proximal CCA intervention to D) symptomatic CEA in combination with proximal CCA intervention. The positivity rate for the combined outcome of perioperative ischemic neurological event and 90 day mortality was 2.2% amongst asymptomatic CEA in isolation, 4.1% amongst symptomatic CEA in isolation, 4.4% amongst asymptomatic CEA in combination with proximal CCA intervention; and 8.8% in patients with symptomatic lesions undergoing combined CEA with proximal CCA intervention. On multivariable analysis patients undergoing CEA with proximal CCA endovascular intervention experienced greater risk for perioperative neurological ischemic event (aOR 2.03, 1.43-2.90, P < .001), combined perioperative neurological ischemic event and 90day mortality (aOR 2.13, 1.62-2.80, P < .001), long term mortality (HR 1.62, 1.12-2.29, P < .001), and cumulative neurological ischemic event in long term follow up (HR 1.62, 1.12-2.29, P = .007). Amongst 4395 cumulative ischemic neurological events in all study patients, 34% were TIA. Carotid bifurcation endarterectomy in combination with proximal endovascular common carotid artery intervention caries an over two fold higher perioperative risk of neurologic ischemic event and 90 day mortality relative to CEA in isolation for asymptomatic and symptomatic cohorts respectively. After surgery, freedom from cerebral ischemia and mortality for patients undergoing dual intervention is closely aligned with patients undergoing CEA in isolation. Despite high adverse perioperative event rates for the combined CEA and CCA treatment, there is likely long term stroke reduction and mortality benefit to this approach in symptomatic patients based on the event free rates seen herein after initial hospital discharge. The benefit of treating asymptomatic tandem ICA and CCA lesions remains vague but the 4.4% perioperative neurologic event and death rate suggests that these patients would be better managed with medical therapy.

Anesthetic management of children with medically refractory pulmonary hypertension undergoing surgical Potts shunt.

Pulmonary hypertension in children is associated with high rates of adverse events under anesthesia. In children who have failed medical therapy, a posttricuspid shunt such as a Potts shunt can offload the right ventricle and possibly delay or replace the need for lung transplantation. Intraoperative management of this procedure, during which an anastomosis between the pulmonary artery and the descending aorta is created, is complex and requires a deep understanding of the pathophysiology of acute and chronic right ventricular failure. This retrospective case review describes the intraoperative management of children undergoing surgical creation of a Potts shunt at a single center. A retrospective case review of all patients under the age of 18 who underwent Potts shunt between April 2013 and June 2022. Medical records were examined, and clinical data of demographics, intraoperative vital signs, anesthetic management, and postoperative outcomes were extracted. Twenty-nine children with medically refractory pulmonary hypertension underwent surgical Potts shunts with a median age of 12 years (range 4 months to 17.4 years). Nineteen Potts shunts (65%) were placed via thoracotomy and 10 (35%) were placed via median sternotomy with use of cardiopulmonary bypass. Ketamine was the most frequently utilized induction agent (17 out of 29, 59%), and the majority of patients were initiated on vasopressin prior to intubation (20 out of 29, 69%). Additional inotropic support with epinephrine (45%), milrinone (28%), norepinephrine (17%), and dobutamine (14%) was used prior to shunt placement. Following opening of the Potts shunt, hemodynamic support was continued with vasopressin (66%), epinephrine (62%), milrinone (59%), dobutamine (14%), and norepinephrine (10%). Major intraoperative complications included severe hypoxemia (21 out of 29, 72%) and hypotension requiring boluses of epinephrine (10 out of 29, 34.5%) but no patient suffered intraoperative cardiac arrest. There were four in-hospital mortalities. A Potts shunt offers another palliative option for children with medically refractory pulmonary hypertension. General anesthesia in these children carries high risk for pulmonary hypertensive crises. Anesthesiologists must understand underlying physiological mechanisms responsble for acute hemodynaic decompensation during acute pulmonary hypertneisve crises. Severe physiological perturbations imposed by thoracic surgery and use of cardiopulmonay bypass can be mitigated by aggresive heodynamic support of ventricle function and maintainence of systemic vascular resistance. Early use of vasopressin, before or immidiately after anesthesia induction, in combination with other inotropes is a useful agent during the perioperative care of thes. Early use of vasopressin during anesthesia induction, and aggressive inotropic support of right ventricular function can help mitigate effects of induction and intubation, single-lung ventilation, and cardiopulmonary bypass. Our single center expereince shows that the Potts shunt surgery, despite high short-term mortaility, may offer another option for palliation in children with medically refractory pulmonary hypertension.

Safety and Performance of the Aortix Device in Acute Decompensated Heart Failure and Cardiorenal Syndrome

BackgroundCardiorenal syndrome (CRS) complicates 33% of acute decompensated heart failure (ADHF) admissions, and patients with persistent congestion at discharge have high 30-day event rates. ObjectivesThe purpose of this study was to evaluate a novel catheter-deployed intra-aortic entrainment pump (IAEP) in patients with ADHF with CRS and persistent congestion. MethodsA multicenter (n = 14), nonrandomized, single-arm, safety and feasibility study of IAEP therapy was conducted. Within patient changes (post–pre IAEP therapy) in fluid loss, hemodynamics, patient-reported dyspnea, and serum biomarkers were assessed using Wilcoxon signed-rank testing. ResultsOf 21 enrolled patients, 18 received Aortix therapy. Mean ± SD patient age was 60.3 ± 7.9 years. The median left ventricular ejection fraction was 22.5% (25th-75th percentile: 10.0%-53.5%); 27.8% had a left ventricular ejection fraction ≥50%. Pre-therapy, patients received 8.7 ± 4.1 days of loop diuretic agents and 44% were on inotropes. Pump therapy averaged 4.6 ± 1.6 days, yielding net fluid losses of 10.7 ± 6.5 L (P < 0.001) and significant (P < 0.01) reductions in central venous pressure (change from baseline: −8.5 mm Hg [25th-75th percentile: −3.5 to −10.0 mm Hg]), pulmonary capillary wedge pressure (−11.0 mm Hg [25th-75th percentile: −5.0 to −14.0 mm Hg]), and serum creatinine (−0.2 mg/dL [25th-75th percentile: −0.1 to −0.5 mg/dL]) with improved estimated glomerular filtration rate (+5.0 mL/min/1.73 m2 [25th-75th percentile: 2.0-9.0 mL/min/1.73 m2]) and patient-reported dyspnea score (+16 [25th-75th percentile: 3-37]). Dyspnea scores, natriuretic peptides, and renal function improvements persisted through 30 days. ConclusionsThis pilot study of patients with ADHF, persistent congestion, and worsening renal function due to CRS supports the potential for safely achieving decongestion using IAEP therapy. These initial promising results provide the basis for future randomized clinical trials of this novel pump. (An Evaluation of the Safety and Performance of the Aortix System for Intra-Aortic Mechanical Circulatory Support in Patients with Cardiorenal Syndrome [The Aortix CRS Pilot Study]; NCT04145635)

Psychiatric or Drug Hospitalizations in Older Cancer Survivors on Long-Term Opioids

Non-cancer patients prescribed chronic courses of opioids are at high risk of psychiatric or drug overdose particularly during the post-tapering period, but data are limited on this effect in cancer survivors. This study quantified emergency room visits or hospital admissions for psychiatric or drug/alcohol overdose/withdrawal (henceforth "events") in cancer survivors prescribed opioids related to their cancer diagnoses. We identified 15,002 cancer survivors in SEER-Medicare diagnosed between 2010 and 2017 with bladder, breast, colon/rectal, kidney, lung, head/neck, or prostate cancer who were prescribed at least 6 months of stable opioids following their cancer diagnosis. The post-tapering interval was defined as a 3-month period following monthly oral morphine equivalent (OME) reduction of at least 15%. Outcomes were studied with logistic regression and time-dependent analysis was performed using a generalized estimating equation (GEE) using an auto-regressive correlation matrix; all reported p-values are two-sided. The study had a median follow up of 24 months; in this time, 8,311 patients (55%) initiated a taper at some point. The mean daily OME in non-tapering patients was 33.4 mg compared to 47.4 mg in tapering patients (p < 0.001); both groups had a low rate of any prior events in the baseline period (7.5% versus 8%, respectively p = 0.686). Patients attempting a taper also tended to be younger (40.3% versus 35.2% age 66-70, p <0.001). There was no difference by race. Opioid tapering was not associated with a higher rate of events in the 3-month post-taper period (p = 0.81) when correcting for sex, primary care site, baseline event rate, comorbidity, and age. Many older cancer survivors who are prescribed chronic opioids remain on high doses of opioids after completing therapy. These patients are at risk of acute psychiatric and drug-related emergencies. Unlike the general population, this risk does not appear to be exacerbated in the months following opioid tapering. Oncologists should be mindful of psychiatric and drug-related events in long-term cancer survivors prescribed chronic opioids, and these data should reassure physicians deciding whether or not to initiate an opioid taper. Future research should explore risk mitigation in these patients.

Coronary Computed Tomographic Angiography With Fractional Flow Reserve in Patients With Type 2 Myocardial Infarction

BackgroundType 2 myocardial infarction (T2MI) related to a supply/demand imbalance of coronary blood flow is common and associated with poor prognosis. Coronary artery disease (CAD) may predispose some individuals to T2MI and contribute to its high rate of recurrent cardiovascular events. Little is known about the presence and extent of CAD in this population. ObjectivesThe goal of this study was to evaluate the presence and characteristics of CAD among patients with T2MI. MethodsIn this prospective study, consecutive eligible individuals with Fourth Universal Definition of Myocardial Infarction criteria for T2MI were enrolled. Participants underwent coronary computed tomography angiography (CTA), fractional flow reserve derived with coronary CTA (FFRCT), and plaque volume analyses. ResultsAmong 50 participants, 25 (50%) were female, and the mean age was 68.0 ± 11.4 years. Atherosclerotic risk factors were common. Coronary CTA revealed coronary plaque in 46 participants (92%). A moderate or greater stenosis (≥50%) was identified in 42% of participants, and obstructive disease (≥50% left main stenosis or ≥70% stenosis in any other epicardial coronary artery) was present in 26%. Prevalence of obstructive CAD did not differ according to T2MI cause (P = 0.54). A hemodynamically significant focal stenosis identified by FFRCT was present in 13 participants (26%). Among participants with a stenosis ≥50% (n = 21), FFRCT excluded lesion-specific hemodynamically significant stenosis in 8 cases (38%). ConclusionsAmong individuals with adjudicated T2MI, CAD was prevalent, but the majority of patients had nonobstructive CAD. Mediators of ischemia are likely multifactorial in this population. (Defining the Prevalence and Characteristics of Coronary Artery Disease Among Patients with Type 2 Myocardial Infarction using CT-FFR [DEFINE TYPE 2 MI]; NCT04864119)

Switching from intravenous vancomycin to oral antibiotics reduces adverse events in a retrospective cohort of outpatients with orthopedic infections.

Vancomycin is frequently used for prolonged courses in treating osteoarticular infections despite a high rate of adverse drug events (ADE). The objective of this study was to evaluate the safety and effectiveness of transitioning to oral therapy compared to continuing parenteral vancomycin in patients with orthopedic infections. We conducted a single-center, retrospective cohort study of patients with orthopedic infections discharged on parenteral vancomycin with a planned duration of at least four weeks. We compared rates of ADE while on vancomycin to rates of ADE after switching to an oral regimen. As a secondary analysis, we compared unplanned hospital readmission within 60 days and treatment failure at one year between patients who were transitioned to oral antibiotics within four weeks of vancomycin initiation and those that were not. Two hundred twenty-eight patients met inclusion criteria. Vancomycin was associated with significantly greater toxicity compared to oral regimens. Fifty-one patients had an adverse event while on vancomycin (5.87 ADE per 1000 patient-days) while 9 patients had an adverse event on oral therapy (1.49 ADE per 1000 patient-days) (Rate difference 4.39 per 1000 patient days, 95% CI: 2.52 to 6.26 events per 1000 patient-days). In proportional hazards analysis, transition to an oral antibiotic regimen was independently associated with a lower rate of ADE (aHR 0.12, 95% CI: 0.02-0.86). Forty-one patients (18%) were transitioned to oral therapy within four weeks; these patients did not have an increased rate of unplanned readmission (12.2% vs 17.1%) or treatment failure (17.1% vs 21.9%). Patients transitioned to oral therapy within 4 weeks of discharge had significantly fewer adverse events and similar incidences of one-year treatment failure compared to patients maintained on parenteral vancomycin. Substituting oral antibiotics for parenteral vancomycin is a potential strategy to minimize vancomycin toxicity during the treatment of orthopedic infections.

Temporal Association Among Influenza-Like Illness, Cardiovascular Events, and Vaccine Dose in Patients With High-Risk Cardiovascular Disease

Influenza-like illness (ILI) activity has been associated with increased risk of cardiopulmonary (CP) events during the influenza season. High-dose trivalent influenza vaccine was not superior to standard-dose quadrivalent vaccine for reducing these events in patients with high-risk cardiovascular (CV) disease in the Influenza Vaccine to Effectively Stop Cardio Thoracic Events and Decompensated Heart Failure (INVESTED) trial. To evaluate whether high-dose trivalent influenza vaccination is associated with benefit over standard-dose quadrivalent vaccination in reducing CP events during periods of high, local influenza activity. This study was a prespecified secondary analysis of INVESTED, a multicenter, double-blind, active comparator randomized clinical trial conducted over 3 consecutive influenza seasons from September 2016 to July 2019. Follow-up was completed in July 2019, and data were analyzed from September 21, 2016, to July 31, 2019. Weekly Centers for Disease Control and Prevention (CDC)-reported, state-level ILI activity was ascertained to assess the weekly odds of the primary outcome. The study population included 3094 patients with high-risk CV disease from participating centers in the US. Participants were randomized to high-dose trivalent or standard-dose quadrivalent influenza vaccine and revaccinated for up to 3 seasons. The primary outcome was the time to composite of all-cause death or CP hospitalization within each season. Additional measures included weekly CDC-reported ILI activity data by state. Among 3094 participants (mean [SD] age, 65 [12] years; 2309 male [75%]), we analyzed 129 285 person-weeks of enrollment, including 1396 composite primary outcome events (1278 CP hospitalization, 118 deaths). A 1% ILI increase in the prior week was associated with an increased risk in the primary outcome (odds ratio [OR], 1.14; 95% CI, 1.07-1.21; P < .001), CP hospitalization (OR, 1.13; 95% CI, 1.06-1.21; P < .001), and CV hospitalization (OR, 1.12; 95% CI, 1.04-1.19; P = .001), after adjusting for state, demographic characteristics, enrollment strata, and CV risk factors. Increased ILI activity was not associated with all-cause death (OR, 1.00; 95% CI, 0.88-1.13; P > .99). High-dose compared with standard-dose vaccine did not significantly reduce the primary outcome, even when the analysis was restricted to weeks of high ILI activity (OR, 0.88; 95% CI, 0.65-1.20; P = .43). Traditionally warmer months in the US were associated with lower CV risk independent of local ILI activity. In this secondary analysis of a randomized clinical trial, ILI activity was temporally associated with increased CP events in patients with high-risk CV disease, and a higher influenza vaccine dose did not significantly reduce temporal CV risk. Other seasonal factors may play a role in the coincident high rates of ILI and CV events. ClinicalTrials.gov Identifier: NCT02787044.

Fractional Flow Reserve–Negative High-Risk Plaques and Clinical Outcomes After Myocardial Infarction

Even after fractional flow reserve (FFR)-guided complete revascularization, patients with myocardial infarction (MI) have high rates of recurrent major adverse cardiovascular events (MACE). These recurrences may be caused by FFR-negative high-risk nonculprit lesions. To assess the association between optical coherence tomography (OCT)-identified high-risk plaques of FFR-negative nonculprit lesions and occurrence of MACE in patients with MI. PECTUS-obs (Identification of Risk Factors for Acute Coronary Events by OCT After STEMI [ST-segment elevation MI] and NSTEMI [non-STEMI] in Patients With Residual Non-flow Limiting Lesions) is an international, multicenter, prospective, observational cohort study. In patients presenting with MI, OCT was performed on all FFR-negative (FFR > 0.80) nonculprit lesions. A high-risk plaque was defined containing at least 2 of the following prespecified criteria: (1) a lipid arc at least 90°, (2) a fibrous cap thickness less than 65 μm, and (3) either plaque rupture or thrombus presence. Patients were enrolled from December 14, 2018, to September 15, 2020. Data were analyzed from December 2, 2022, to June 28, 2023. The primary end point of MACE, a composite of all-cause mortality, nonfatal MI, or unplanned revascularization, at 2-year follow-up was compared in patients with and without a high-risk plaque. A total of 438 patients were enrolled, and OCT findings were analyzable in 420. Among included patients, mean (SD) age was 63 (10) years, 340 (81.0) were men, and STEMI and non-STEMI were equally represented (217 [51.7%] and 203 [48.3%]). A mean (SD) of 1.17 (0.42) nonculprit lesions per patient was imaged. Analysis of OCT images revealed at least 1 high-risk plaque in 143 patients (34.0%). The primary end point occurred in 22 patients (15.4%) with a high-risk plaque and 23 of 277 patients (8.3%) without a high-risk plaque (hazard ratio, 1.93 [95% CI, 1.08-3.47]; P = .02), primarily driven by more unplanned revascularizations in patients with a high-risk plaque (14 of 143 [9.8%] vs 12 of 277 [4.3%]; P = .02). Among patients with MI and FFR-negative nonculprit lesions, the presence of a high-risk plaque is associated with a worse clinical outcome, which is mainly driven by a higher number of unplanned revascularizations. In a population with a high recurrent event rate despite physiology-guided complete revascularization, these results call for research on additional pharmacological or focal treatment strategies in patients harboring high-risk plaques.

Toxicity spectrum and risk factors for chemo-immunotherapy in locally advanced or metastatic lung cancer.

Chemo-immunotherapy has become the best first-line treatment for advanced lung cancer patients without oncogenic drivers. However, it may also lead to an increased incidence and severity of treatment-related adverse events. In this retrospective study, lung cancer patients administrated with either anti-PD-1 or anti-PD-L1 treatment plus chemotherapy were included. Data on demographic characteristics, disease characteristics, treatment strategies, laboratory results, and clinical outcomes were collected from the Electronic Medical Records System and evaluation scales. Chi-square, univariate, and multivariate logistic regression analyses were used to identify the risk factors for immune-related adverse events (irAEs). A total of 116 patients were included in the study, and the majority experienced treatment-related adverse events. Adverse events of any grade were reported in 114 (98.3%) patients, with 73 (62.9%) experiencing Grade 3 or higher events. The most frequent adverse events were anemia (67.2%), decreased appetite (62.9%), and alopecia (53.4%). Fifty-four (46.6%) patients were diagnosed with irAEs, with hypothyroidism (28.4%) being the most commonly reported. Multivariable analysis demonstrated a significant correlation between the number of treatment cycles, elevated baseline levels of thyroid stimulating hormone (TSH) and interleukin-6 (IL-6) with irAEs (OR = 1.222, P = 0.009, OR = 1.945, P = 0.016, OR = 1.176, P = 0.004), and IL-6 was identified as a strong predictor of severe irAEs (OR = 1.084, P = 0.014). Our study demonstrated the safety of chemo-immunotherapy in lung cancer patients without additional toxicity. The number of treatment cycles, higher baseline levels of TSH and IL-6 were identified as potential clinical biomarkers for irAEs.

Left atrial function index predicts poor outcomes in acute myocardial infarction patients treated with percutaneous coronary intervention.

The left atrial function index (LAFI) is an index that combines the left atrial emptying fraction, adjusted left atrial volume and stroke volume. The prognostic value of LAFI in acute myocardial infarction (AMI) patients treated with percutaneous coronary intervention (PCI) is unknown. This study aims to determine whether LAFI predicts prognosis in AMI patients treated with PCI. Patients with newly diagnosed AMI who were treated with PCI at Hunan Provincial People's Hospital from March 2020 to October 2021 were prospectively enrolled. All patients underwent transthoracic echocardiography (TTE) at baseline and follow-up. The endpoint events included rehospitalization due to unstable angina, nonfatal myocardial infarction, rehospitalization due to heart failure and cardiovascular death. A total of 368 patients with AMI (92 women; mean age, 61.45 ± 11.91 years) were studied with a median follow-up of 14 ± 6.58 months. Sixty-nine patients had endpoint events. Patients who presented with events had a significantly lower LAFI than patients without events (34.25 ± 12.86 vs. 48.38 ± 19.42, P < 0.0001). Multivariate Cox analysis demonstrated that LAFI (HR = 0.97 [95% CI: 0.95; 0.99]; P = 0.012) and the Killip classification (HR = 1.51 [95% CI: 1.03; 2.22]; P = 0.034) were independently predictive of endpoint events. Kaplan-Meier survival curves showed that patients with LAFI ≤ 40.17 cm/ml/m2 had higher events than patients with LAFI > 40.17 cm/ml/m2 (HR = 8.53 [95% CI: 4.74; 15.35]; P < 0.0001). LAFI is a strong and independent predictor of adverse events and can be used for risk stratification in patients with AMI treated with PCI.

Abstract 085: Monocytes-derived Cytokines Induce Endothelial Dysfunction In Primary Aldosteronism

Due to aldosterone excess and its pleotropic effects, patients with primary aldosteronism (PA) are exposed to high rates of cardiovascular events. Endothelial dysfunction is the first step in the development of vascular disease and monocytes are an important immune cell type inducing vascular damage. Therefore, we measured endothelial function between PA patients and healthy controls and analyzed the impact of monocytes-derived cyctokines on the development of endothelial dysfunction. Endothelial function was measured in 13 healthy controls, 42 PA patients before and in 22 patients 6 months after initiation of a specific treatment using flow mediated dilation method (FMD). Monocytes were isolated from 6 healthy individuals as well as from 8 PA patients before and treatment. Cytokine profile was measured by a Human Cytokine 17-plex Assay (Bio-rad). The effects of monocyte-derived cytokines on endothelial function were studied by wire myography in pre-constricted thoracic aortic pieces of healthy mice. FMD was significantly lower among PA patients compared to controls. Surgical or pharmacological treatment significantly improved endothelial function in PA patients. Monocytes from untreated patients with PA secreted significantly higher concentrations of the following cytokines and growth factors than healthy controls: G-CSF, IFN-γ, TNF-α, IL-6, IL-10, IL-8, IL-17, and MCP-1. Especially concentrations of IL-6 (388 (351-580)pg/ml vs. 36(4-268)pg/ml, p&lt;0.05) and TNF-α (95(48-135)pg/ml vs 17(5-41)pg/ml, p&lt;0.05) were much higher among PA patients. In pre-constricted murine aortas, 24 hours incubation of the secretome from untreated patients with PA induced an impaired endothelial vasodilation compared to the secretome of the controls. Interestingly, in comparison to untreated patients, treatment of PA not only reduced monocytes-derived cytokine levels, but also improved endothelial dysfunction in pre-constricted aortas incubated with the corresponding secretome. Endothelial function is impaired in PA. This impairment seem to be in part mediated by an increased release of pro-inflammatory cytokines from monocytes. PA treatment reduced the pro-inflammatory activity of monocytes and improved endothelial function.

Underutilization of Mineralocorticoid Antagonists in Patients With Heart Failure With Reduced Ejection Fraction

BackgroundIt is unknown how the efficacy and safety of mineralocorticoid receptor antagonists vary according to duration of heart failure with reduced ejection fraction (HFrEF). ObjectivesIn this study, we sought to evaluate the safety and efficacy of eplerenone according to duration of HFrEF. MethodsIn the EMPHASIS-HF trial, 3 patient groups were created according to HFrEF duration: <1 year, 1 to <5 years, and ≥5 years. The primary outcome was the composite of heart failure (HF) hospitalization or cardiovascular death. Outcomes were adjusted for prespecified prognostic variables and examined with the use of Cox regression models. ResultsThe numbers of patients in each group were: 975, <1 year; 769, 1 to <5 years; and 988, ≥5 years. Patients with longer-standing HF were older and more frequently had cardiovascular and noncardiovascular comorbidities. The rate of the primary outcome (per 100 person-years) increased with HFrEF duration: 9.8 (95% CI: 8.4-11.4) for <1 year, 13.5 (95% CI: 11.6-15.7) for 1 to <5 years, and 17.6 (95% CI: 15.6-19.8) for ≥5 years. The benefits of eplerenone were consistent across HF duration: HRs for the primary outcome were 0.57 (95% CI: 0.42-0.79) for <1 year, 0.81 (95% CI: 0.60-1.10) for 1 to <5 years, and 0.61 (95% CI: 0.48-0.78) for ≥5 years; Pinteraction = 0.24. The absolute benefit was greatest in the longest-duration group: the number needed to treat for the primary outcome was 14 for <1 year, 13 for 1 to <5 years, and 10 for ≥5 years duration. ConclusionsPatients with longer-standing HFrEF had worse clinical status and a higher rate of events, but the benefit of eplerenone was consistent regardless of HFrEF duration. (A Comparison of Outcomes in Patients in NYHA Class II Heart Failure When Treated With Eplerenone or Placebo in Addition to Standard Heart Failure Medicines [EMPHASIS-HF]; NCT00232180)

ThTP6.5 Long term major adverse cardiovascular events following myocardial injury after non-cardiac surgery (MINS): A systematic review and meta-analysis

Abstract Aims Myocardial injury after non-cardiac surgery (MINS) is diagnosed following asymptomatic troponin elevation in the perioperative period. MINS is associated with high mortality rates and significant rates of major adverse cardiac events (MACE) within the first 30 days following surgery. However, less is known regarding its impact on mortality and morbidity beyond this time. This systematic review and meta-analysis aims to establish the rates of long term morbidity and mortality associated with MINS. Methods This review was registered with PROSPERO (CRD42021283995). Medline, EMBASE and Cochrane CENTRAL were searched, and abstracts screened by two reviewers. Observational studies and control arms of trials reporting mortality and cardiovascular outcomes beyond 30 days in adult patients diagnosed with MINS following non-cardiac surgery were included. Risk of bias was assessed using the Quality in Prognostic Studies tool (QUIPS). A random effects model was used for meta-analysis of outcome subgroups. Results Searches identified 40 studies. Meta-analysis of 37 cohort studies found a rate of MACE associated MINS of 21% and mortality following MINS was 25% at one year follow-up. A non-linear increase in mortality rates was observed up to 1 year post surgery. MACE rates were also lower in elective surgery compared to a subgroup which included emergency cases. Analysis demonstrated a wide variety of accepted MINS and MACE diagnostic criteria within the included studies. Conclusions A diagnosis of MINS is associated with high rates of poor cardiovascular outcomes up to one year. Work is needed to standardise diagnostic criteria and reporting of MINS related outcomes.

Flavor-dependent long-range neutrino interactions in DUNE & T2HK: alone they constrain, together they discover

Discovering new neutrino interactions would represent evidence of physics beyond the Standard Model. We focus on new flavor-dependent long-range neutrino interactions mediated by ultra-light mediators, with masses below 10−10 eV, introduced by new lepton-number gauge symmetries Le – Lμ, Le – Lτ, and Lμ – Lτ. Because the interaction range is ultra-long, nearby and distant matter — primarily electrons and neutrons — in the Earth, Moon, Sun, Milky Way, and the local Universe, may source a large matter potential that modifies neutrino oscillation probabilities. The upcoming Deep Underground Neutrino Experiment (DUNE) and the Tokai-to-Hyper-Kamiokande (T2HK) long-baseline neutrino experiments will provide an opportunity to search for these interactions, thanks to their high event rates and well-characterized neutrino beams. We forecast their probing power. Our results reveal novel perspectives. Alone, DUNE and T2HK may strongly constrain long-range interactions, setting new limits on their coupling strength for mediators lighter than 10−18 eV. However, if the new interactions are subdominant, then both DUNE and T2HK, together, will be needed to discover them, since their combination lifts parameter degeneracies that weaken their individual sensitivity. DUNE and T2HK, especially when combined, provide a valuable opportunity to explore physics beyond the Standard Model.