Vaccine Effectiveness Against Influenza A-Associated Hospitalization, Organ Failure, and Death: United States, 2022-2023.

BACKGROUND: Influenza circulation during the 2022-2023 season in the United States largely returned to pre-coronavirus disease 2019 (COVID-19)-pandemic patterns and levels. Influenza A(H3N2) viruses were detected most frequently this season, predominately clade 3C.2a1b.2a, a close antigenic match to the vaccine strain. METHODS: To understand effectiveness of the 2022-2023 influenza vaccine against influenza-associated hospitalization, organ failure, and death, a multicenter sentinel surveillance network in the United States prospectively enrolled adults hospitalized with acute respiratory illness between 1 October 2022, and 28 February 2023. Using the test-negative design, vaccine effectiveness (VE) estimates against influenza-associated hospitalization, organ failures, and death were measured by comparing the odds of current-season influenza vaccination in influenza-positive case-patients and influenza-negative, SARS-CoV-2-negative control-patients. RESULTS: A total of 3707 patients, including 714 influenza cases (33% vaccinated) and 2993 influenza- and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-negative controls (49% vaccinated) were analyzed. VE against influenza-associated hospitalization was 37% (95% confidence interval [CI]: 27%-46%) and varied by age (18-64 years: 47% [30%-60%]; ≥65 years: 28% [10%-43%]), and virus (A[H3N2]: 29% [6%-46%], A[H1N1]: 47% [23%-64%]). VE against more severe influenza-associated outcomes included: 41% (29%-50%) against influenza with hypoxemia treated with supplemental oxygen; 65% (56%-72%) against influenza with respiratory, cardiovascular, or renal failure treated with organ support; and 66% (40%-81%) against influenza with respiratory failure treated with invasive mechanical ventilation. CONCLUSIONS: During an early 2022-2023 influenza season with a well-matched influenza vaccine, vaccination was associated with reduced risk of influenza-associated hospitalization and organ failure.

Interim Effectiveness of Updated 2023-2024 (Monovalent XBB.1.5) COVID-19 Vaccines Against COVID-19-Associated Emergency Department and Urgent Care Encounters and Hospitalization Among Immunocompetent Adults Aged ≥18 Years - VISION and IVY Networks, September 2023-January 2024.

In September 2023, CDC's Advisory Committee on Immunization Practices recommended updated 2023-2024 (monovalent XBB.1.5) COVID-19 vaccination for all persons aged ≥6 months to prevent COVID-19, including severe disease. However, few estimates of updated vaccine effectiveness (VE) against medically attended illness are available. This analysis evaluated VE of an updated COVID-19 vaccine dose against COVID-19-associated emergency department (ED) or urgent care (UC) encounters and hospitalization among immunocompetent adults aged ≥18 years during September 2023-January 2024 using a test-negative, case-control design with data from two CDC VE networks. VE against COVID-19-associated ED/UC encounters was 51% (95% CI = 47%-54%) during the first 7-59 days after an updated dose and 39% (95% CI = 33%-45%) during the 60-119 days after an updated dose. VE estimates against COVID-19-associated hospitalization from two CDC VE networks were 52% (95% CI = 47%-57%) and 43% (95% CI = 27%-56%), with a median interval from updated dose of 42 and 47 days, respectively. Updated COVID-19 vaccine provided increased protection against COVID-19-associated ED/UC encounters and hospitalization among immunocompetent adults. These results support CDC recommendations for updated 2023-2024 COVID-19 vaccination. All persons aged ≥6 months should receive updated 2023-2024 COVID-19 vaccine.

Effectiveness of Monovalent mRNA COVID-19 Vaccination in Preventing COVID-19-Associated Invasive Mechanical Ventilation and Death Among Immunocompetent Adults During the Omicron Variant Period - IVY Network, 19 U.S. States, February 1, 2022-January 31, 2023.

As of April 2023, the COVID-19 pandemic has resulted in 1.1 million deaths in the United States, with approximately 75% of deaths occurring among adults aged ≥65 years (1). Data on the durability of protection provided by monovalent mRNA COVID-19 vaccination against critical outcomes of COVID-19 are limited beyond the Omicron BA.1 lineage period (December 26, 2021-March 26, 2022). In this case-control analysis, the effectiveness of 2-4 monovalent mRNA COVID-19 vaccine doses was evaluated against COVID-19-associated invasive mechanical ventilation (IMV) and in-hospital death among immunocompetent adults aged ≥18 years during February 1, 2022-January 31, 2023. Vaccine effectiveness (VE) against IMV and in-hospital death was 62% among adults aged ≥18 years and 69% among those aged ≥65 years. When stratified by time since last dose, VE was 76% at 7-179 days, 54% at 180-364 days, and 56% at ≥365 days. Monovalent mRNA COVID-19 vaccination provided substantial, durable protection against IMV and in-hospital death among adults during the Omicron variant period. All adults should remain up to date with recommended COVID-19 vaccination to prevent critical COVID-19-associated outcomes.

Disease Severity of Respiratory Syncytial Virus Compared with COVID-19 and Influenza Among Hospitalized Adults Aged ≥60 Years - IVY Network, 20 U.S. States, February 2022-May 2023.

On June 21, 2023, CDC's Advisory Committee on Immunization Practices recommended respiratory syncytial virus (RSV) vaccination for adults aged ≥60 years, offered to individual adults using shared clinical decision-making. Informed use of these vaccines requires an understanding of RSV disease severity. To characterize RSV-associated severity, 5,784 adults aged ≥60 years hospitalized with acute respiratory illness and laboratory-confirmed RSV, SARS-CoV-2, or influenza infection were prospectively enrolled from 25 hospitals in 20 U.S. states during February 1, 2022-May 31, 2023. Multivariable logistic regression was used to compare RSV disease severity with COVID-19 and influenza severity on the basis of the following outcomes: 1) standard flow (<30 L/minute) oxygen therapy, 2) high-flow nasal cannula (HFNC) or noninvasive ventilation (NIV), 3) intensive care unit (ICU) admission, and 4) invasive mechanical ventilation (IMV) or death. Overall, 304 (5.3%) enrolled adults were hospitalized with RSV, 4,734 (81.8%) with COVID-19 and 746 (12.9%) with influenza. Patients hospitalized with RSV were more likely to receive standard flow oxygen, HFNC or NIV, and ICU admission than were those hospitalized with COVID-19 or influenza. Patients hospitalized with RSV were more likely to receive IMV or die compared with patients hospitalized with influenza (adjusted odds ratio = 2.08; 95% CI = 1.33-3.26). Among hospitalized older adults, RSV was less common, but was associated with more severe disease than COVID-19 or influenza. High disease severity in older adults hospitalized with RSV is important to consider in shared clinical decision-making regarding RSV vaccination.

Renin-Angiotensin System Modulation With Synthetic Angiotensin (1-7) and Angiotensin II Type 1 Receptor-Biased Ligand in Adults With COVID-19: Two Randomized Clinical Trials.

Importance: Preclinical models suggest dysregulation of the renin-angiotensin system (RAS) caused by SARS-CoV-2 infection may increase the relative activity of angiotensin II compared with angiotensin (1-7) and may be an important contributor to COVID-19 pathophysiology. Objective: To evaluate the efficacy and safety of RAS modulation using 2 investigational RAS agents, TXA-127 (synthetic angiotensin [1-7]) and TRV-027 (an angiotensin II type 1 receptor-biased ligand), that are hypothesized to potentiate the action of angiotensin (1-7) and mitigate the action of the angiotensin II. Design, Setting, and Participants: Two randomized clinical trials including adults hospitalized with acute COVID-19 and new-onset hypoxemia were conducted at 35 sites in the US between July 22, 2021, and April 20, 2022; last follow-up visit: July 26, 2022. Interventions: A 0.5-mg/kg intravenous infusion of TXA-127 once daily for 5 days or placebo. A 12-mg/h continuous intravenous infusion of TRV-027 for 5 days or placebo. Main Outcomes and Measures: The primary outcome was oxygen-free days, an ordinal outcome that classifies a patient's status at day 28 based on mortality and duration of supplemental oxygen use; an adjusted odds ratio (OR) greater than 1.0 indicated superiority of the RAS agent vs placebo. A key secondary outcome was 28-day all-cause mortality. Safety outcomes included allergic reaction, new kidney replacement therapy, and hypotension. Results: Both trials met prespecified early stopping criteria for a low probability of efficacy. Of 343 patients in the TXA-127 trial (226 [65.9%] aged 31-64 years, 200 [58.3%] men, 225 [65.6%] White, and 274 [79.9%] not Hispanic), 170 received TXA-127 and 173 received placebo. Of 290 patients in the TRV-027 trial (199 [68.6%] aged 31-64 years, 168 [57.9%] men, 195 [67.2%] White, and 225 [77.6%] not Hispanic), 145 received TRV-027 and 145 received placebo. Compared with placebo, both TXA-127 (unadjusted mean difference, -2.3 [95% CrI, -4.8 to 0.2]; adjusted OR, 0.88 [95% CrI, 0.59 to 1.30]) and TRV-027 (unadjusted mean difference, -2.4 [95% CrI, -5.1 to 0.3]; adjusted OR, 0.74 [95% CrI, 0.48 to 1.13]) resulted in no difference in oxygen-free days. In the TXA-127 trial, 28-day all-cause mortality occurred in 22 of 163 patients (13.5%) in the TXA-127 group vs 22 of 166 patients (13.3%) in the placebo group (adjusted OR, 0.83 [95% CrI, 0.41 to 1.66]). In the TRV-027 trial, 28-day all-cause mortality occurred in 29 of 141 patients (20.6%) in the TRV-027 group vs 18 of 140 patients (12.9%) in the placebo group (adjusted OR, 1.52 [95% CrI, 0.75 to 3.08]). The frequency of the safety outcomes was similar with either TXA-127 or TRV-027 vs placebo. Conclusions and Relevance: In adults with severe COVID-19, RAS modulation (TXA-127 or TRV-027) did not improve oxygen-free days vs placebo. These results do not support the hypotheses that pharmacological interventions that selectively block the angiotensin II type 1 receptor or increase angiotensin (1-7) improve outcomes for patients with severe COVID-19. Trial Registration: ClinicalTrials.gov Identifier: NCT04924660.

Clinical characteristics and prognosis of patients with microvascular angina: an international and prospective cohort study by the Coronary Vasomotor Disorders International Study (COVADIS) Group.

AIMS: To provide multi-national, multi-ethnic data on the clinical characteristics and prognosis of patients with microvascular angina (MVA). METHODS AND RESULTS: The Coronary Vasomotor Disorders International Study Group proposed the diagnostic criteria for MVA. We prospectively evaluated the clinical characteristics of patients according to these criteria and their prognosis. The primary endpoint was the composite of major cardiovascular events (MACE), verified by institutional investigators, which included cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, and hospitalization due to heart failure or unstable angina. During the period from 1 July 2015 to 31 December 2018, 686 patients with MVA were registered from 14 institutes in 7 countries from 4 continents. Among them, 64% were female and the main ethnic groups were Caucasians (61%) and Asians (29%). During follow-up of a median of 398 days (IQR 365-744), 78 MACE occurred (6.4% in men vs. 8.6% in women, P = 0.19). Multivariable Cox proportional hazard analysis disclosed that hypertension and previous history of coronary artery disease (CAD), including acute coronary syndrome and stable angina pectoris, were independent predictors of MACE. There was no sex or ethnic difference in prognosis, although women had lower Seattle Angina Questionnaire scores than men (P < 0.05). CONCLUSIONS: This first international study provides novel evidence that MVA is an important health problem regardless of sex or ethnicity that a diagnosis of MVA portends a substantial risk for MACE associated with hypertension and previous history of CAD, and that women have a lower quality of life than men despite the comparable prognosis.

Cardiovascular Considerations in Caring for Pregnant Patients: A Scientific Statement From the American Heart Association.

Cardio-obstetrics has emerged as an important multidisciplinary field that requires a team approach to the management of cardiovascular disease during pregnancy. Cardiac conditions during pregnancy include hypertensive disorders, hypercholesterolemia, myocardial infarction, cardiomyopathies, arrhythmias, valvular disease, thromboembolic disease, aortic disease, and cerebrovascular diseases. Cardiovascular disease is the primary cause of pregnancy-related mortality in the United States. Advancing maternal age and preexisting comorbid conditions have contributed to the increased rates of maternal mortality. Preconception counseling by the multidisciplinary cardio-obstetrics team is essential for women with preexistent cardiac conditions or history of preeclampsia. Early involvement of the cardio-obstetrics team is critical to prevent maternal morbidity and mortality during the length of the pregnancy and 1 year postpartum. A general understanding of cardiovascular disease during pregnancy should be a core knowledge area for all cardiovascular and primary care clinicians. This scientific statement provides an overview of the diagnosis and management of cardiovascular disease during pregnancy.

Is microvascular dysfunction a systemic disorder with common biomarkers found in the heart, brain, and kidneys? - A scoping review.

Although microvascular dysfunction (MVD) has been well characterized in individual organs as different disease entities, clinical evidence is mounting in support of an underlying systemic process. To address this hypothesis, we systematically searched PubMed and Medline for studies in adults published between 2014 and 2019 that measured blood biomarkers of MVD in three vital organs i.e. brain, heart, and the kidney. Of the 9706 unique articles 321 met the criteria, reporting 49 biomarkers of which 16 were common to the three organs. Endothelial dysfunction, inflammation including reactive oxidation, immune activation, and coagulation were the commonly recognized pathways. Triglyceride, C-reactive protein, Cystatin C, homocysteine, uric acid, IL-6, NT-proBNP, thrombomodulin, von Willebrand Factor, and uric acid were increased in MVD of all three organs. In contrast, vitamin D was decreased. Adiponectin, asymmetric dimethylarginine, total cholesterol, high-density and low-density cholesterol were found to be variably increased or decreased in studies. We review the pathways underlying MVD in the three organs and summarize evidence supporting its systemic nature. This scoping review informs clinicians and researchers in the multi-system manifestation of MVD. Future work should focus on longitudinal investigations to evaluate the multi-system involvement of this disease.

Use of peripheral arterial tonometry in detection of abnormal coronary flow reserve.

BACKGROUND: We assessed the utility of EndoPAT, a device that measures reactive hyperemia index (RHI) as a clinical screening tool for identifying low coronary flow reserve (CFR). Distinguishing normal from low CFR aids assessment for coronary microvascular dysfunction (CMD) or large vessel coronary artery disease (CAD). METHODS: From June 2014-May 2019, in a convenience sample, we measured RHI in adults undergoing clinically indicated cardiac Rubidium-82 positron emission tomography/computed tomography (PET/CT) at a single center. Exclusion criteria were inability to consent, lack of English proficiency, and physical limitation. We defined low RHI as <1.67 and low CFR as <2.5. Distribution of RHI was skewed so we used its natural logarithm (LnRHI) to calculate Pearson correlation and area under the curve (AUC). RESULTS: Of 265 patients with PET/CT, we enrolled 131, and 100 had adequate data. Patients had a mean age of 61 years (SD = 12), 46% were female, 29% non-white. Thirty-six patients had low RHI, and 60 had depressed CFR. LnRHI did not distinguish patients with low from normal CFR (AUC = 0.53; 95% Cl, 0.41-0.64) and did not correlate with CFR (r = -0.021, p = 0.83). Low RHI did not distinguish patients with traditional CAD risk factors, presence of calcification, or perfusion defect (p > 0.05). Conversely, mean augmentation index, a measure of arterial stiffness, was higher with low RHI (p = 0.005) but not CFR (p = 0.625). RHI was lower in patients we identified as CMD (low CFR, no perfusion defect and calcium score of 0) (1.88 versus 2.21, p = 0.35) although we were underpowered (n = 12) to meet statistical significance. CONCLUSIONS: Peripheral RHI is insufficient as a clinical screening tool for low CFR as measured by cardiac PET/CT. Differences in vascular pathology assessed by each method may explain this finding.

Utility of discovery approach using proteomics to create a biomarker profile for coronary microvascular dysfunction.

INTRODUCTION: Coronary microvascular dysfunction (CMD) is a complex disease, difficult to diagnose and often requires advanced imaging. We used mass spectrometry (MS) using discovery approach to search for serum proteins as potential biomarkers in these patients. METHODS: We used serum samples from 10 patients with CMD and 10 with normal coronary flow reserve (CFR) admitted to an observation unit where acute myocardial infarction was excluded. We identified CMD using 82Rb positron emission tomography/computed tomography as CFR <2 in response to regadenoson, in the absence of coronary calcification or regional perfusion defects. We used MS to identify potential protein biomarkers that were differentially expressed in cases and controls. RESULTS: Baseline characteristics were not different between cases and controls, except for beta-blocker use and which was higher in cases, and mean (SD) CFR which was lower in cases [1.19 (0.23) and 2.78 (0.78) in cases and controls respectively; p < 0.01]. We identified 5345 peptides corresponding to 209 proteins, and identified 197 proteins by peptides with suitable properties to infer relative quantitation values. While the calculated values for some proteins (e.g. vascular cell adhesion molecule-1, apolipoprotein C and Von Willebrand Factor) indicate fold-differences between groups, these are most likely a result of high values in only 1-2 patients and are not statistically significant. CONCLUSION: Mass spectrometry using discovery approach may not be an adequate method for quantitative assessment of serum proteins in CMD patients. Future MS studies should evaluate other approaches including tissue samples or serial measurements.

Sex Differences in the Presentation and Perception of Symptoms Among Young Patients With Myocardial Infarction: Evidence from the VIRGO Study (Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients).

BACKGROUND: Some studies report that women are less likely to present with chest pain for acute myocardial infarction (AMI). Information on symptom presentation, perception of symptoms, and care-seeking behaviors is limited for young patients with AMI. METHODS: We interviewed 2009 women and 976 men aged 18 to 55 years hospitalized for AMI at 103 US hospitals participating in the VIRGO study (Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients). Structured patient interviews during the index AMI hospitalization were used to collect information on symptom presentation, perception of symptoms, and care-seeking behaviors. We compared patient characteristics and presentation information by sex. Multivariable hierarchical logistic regression was used to evaluate the association between sex and symptom presentation. RESULTS: The majority of women (87.0%) and men (89.5%) presented with chest pain (defined as pain, pressure, tightness, or discomfort). Women were more likely to present with ≥3 associated symptoms than men (eg, epigastric symptoms, palpitations, and pain or discomfort in the jaw, neck, arms, or between the shoulder blades; 61.9% for women versus 54.8% for men, P<0.001). In adjusted analyses, women with an ST-segment-elevation AMI were more likely than men to present without chest pain (odds ratio, 1.51; 95% confidence interval, 1.03-2.22). In comparison with men, women were more likely to perceive symptoms as stress/anxiety (20.9% versus 11.8%, P<0.001) but less likely to attribute symptoms to muscle pain (15.4% versus 21.2%, P=0.029). Approximately 29.5% of women and 22.1% of men sought medical care for similar symptoms before their hospitalization (P<0.001); however, 53% of women reported that their provider did not think these symptoms were heart-related in comparison with 37% of men (P<0.001). CONCLUSIONS: The presentation of AMI symptoms was similar for young women and men, with chest pain as the predominant symptom for both sexes. Women presented with a greater number of additional non-chest pain symptoms regardless of the presence of chest pain, and both women and their healthcare providers were less likely to attribute their prodromal symptoms to heart disease in comparison with men.

Spontaneous rupture of the ascending aorta.

BACKGROUND: Nontraumatic, spontaneous rupture of the ascending aorta is rare and the etiology is largely unknown. METHODS: We reviewed seven patients from our institution, with no known aortic disease or hereditary connective tissue disorder that presented with spontaneous ascending aortic rupture from 2012 to 2017. RESULTS: Most patients presented with non-radiating chest pain along with hypertension (71.4%). The mean ascending aortic diameter at rupture was 4.60 ± 0.62 cm. The median door-to-operating room time was 2.58 h, resulting from effective implementation of an aortic emergency protocol. There were no operative mortalities. CONCLUSIONS: In patients with ascending aortic rupture, aortic diameter may not always correlate with the risk of rupture. Rapid diagnosis combined with a multidisciplinary approach is vital for the successful management of these high-risk patients.

Depression is associated with recurrent chest pain with or without coronary artery disease: A prospective cohort study in the emergency department.

BACKGROUND: Only a small fraction of acute chest pain in the emergency department (ED) is due to obstructive coronary artery disease (CAD). ED chest pain remains associated with high rates of recidivism, often in the presence of nonobstructive CAD. Psychological states such as depression, anxiety, and elevation of perceived stress may account for this finding. The objective of the study was to determine whether psychological states predict recurrent chest pain (RCP). METHODS: We conducted a prospective cohort study of low- to moderate-cardiac risk ED patients admitted to the Yale Chest Pain Center with acute chest pain. Depression, anxiety, and perceived stress were assessed in each patient using multistudy-validated screening scales: Patient Health Questionnaire (PHQ8), Clinical Anxiety Scale (CAS), and Perceived Stress Scale (PSS), respectively. All patients ruled out for infarction underwent appropriate cardiac stress testing. Primary outcome was RCP at 30 days evaluated by phone follow-up and medical record. The relationship between each psychological scale and RCP was evaluated using ordinal logistic regressions, controlling for known sociodemographic and cardiac risk factors. Depression (PHQ8≥10), anxiety (CAS≥30), and perceived stress (PSS≥15) were considered positive. RESULTS: Between August 2013 and May 2015, 985 patients were screened at the Yale Chest Pain Center. Of 500 enrolled patients, 483 patients had complete data and 365 (76%) patients completed follow-up. Thirty-six percent (n=131) had RCP within 1 month. On multivariable regression models, depression (odds ratio [OR]=2.11, 95% CI 1.18-3.79) was a significant independent predictor of 30-day chest pain recurrence after adjustment, whereas PSS (OR=0.96, 95% CI 0.60-1.53) and anxiety (OR=1.59, 95% CI 0.80-3.20) were not. Similarly, there was a direct relationship between psychometric evaluation of depression (via PHQ8) and the frequency of chest pain. CONCLUSIONS: Depression is independently associated with RCP regardless of significant cardiac ischemia on stress testing. Identification and targeted interventions may curtail recidivism with RCP.

Sex differences in reperfusion in young patients with ST-segment-elevation myocardial infarction: results from the VIRGO study.

BACKGROUND: Sex disparities in reperfusion therapy for patients with acute ST-segment-elevation myocardial infarction have been documented. However, little is known about whether these patterns exist in the comparison of young women with men. METHODS AND RESULTS: We examined sex differences in rates, types of reperfusion therapy, and proportion of patients exceeding American Heart Association reperfusion time guidelines for ST-segment-elevation myocardial infarction in a prospective observational cohort study (2008-2012) of 1465 patients 18 to 55 years of age, as part of the US Variations in Recovery: Role of Gender on Outcomes of Young AMI Patients (VIRGO) study at 103 hospitals enrolling in a 2:1 ratio of women to men. Of the 1238 patients eligible for reperfusion, women were more likely to be untreated than men (9% versus 4%, P=0.002). There was no difference in reperfusion strategy for the 695 women and 458 men treated. Women were more likely to exceed in-hospital and transfer time guidelines for percutaneous coronary intervention than men (41% versus 29%; odds ratio, 1.65; 95% confidence interval, 1.27-2.16), more so when transferred (67% versus 44%; odds ratio, 2.63; 95% confidence interval, 1.17-4.07); and more likely to exceed door-to-needle times (67% versus 37%; odds ratio, 2.62; 95% confidence interval, 1.23-2.18). After adjustment for sociodemographic, clinical, and organizational factors, sex remained an important factor in exceeding reperfusion guidelines (odds ratio, 1.72; 95% confidence interval, 1.28-2.33). CONCLUSIONS: Young women with ST-segment-elevation myocardial infarction are less likely to receive reperfusion therapy and more likely to have reperfusion delays than similarly aged men. Sex disparities are more pronounced among patients transferred to percutaneous coronary intervention institutions or who received fibrinolytic therapy.

The Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients (VIRGO) Classification System: A Taxonomy for Young Women With Acute Myocardial Infarction.

BACKGROUND: Current classification schemes for acute myocardial infarction (AMI) may not accommodate the breadth of clinical phenotypes in young women. METHODS AND RESULTS: We developed a novel taxonomy among young adults (≤55 years) with AMI enrolled in the Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients (VIRGO) study. We first classified a subset of patients (n=600) according to the Third Universal Definition of MI using a structured abstraction tool. There was heterogeneity within type 2 AMI, and 54 patients (9%; including 51 of 412 women) were unclassified. Using an inductive approach, we iteratively grouped patients with shared clinical characteristics, with the aims of developing a more inclusive taxonomy that could distinguish unique clinical phenotypes. The final VIRGO taxonomy classified 2802 study participants as follows: class 1, plaque-mediated culprit lesion (82.5% of women; 94.9% of men); class 2, obstructive coronary artery disease with supply-demand mismatch (2a: 1.4% women; 0.9% men) and without supply-demand mismatch (2b: 2.4% women; 1.1% men); class 3, nonobstructive coronary artery disease with supply-demand mismatch (3a: 4.3% women; 0.8% men) and without supply-demand mismatch (3b: 7.0% women; 1.9% men); class 4, other identifiable mechanism (spontaneous dissection, vasospasm, embolism; 1.5% women, 0.2% men); and class 5, undetermined classification (0.8% women, 0.2% men). CONCLUSIONS: Approximately 1 in 8 young women with AMI is unclassified by the Universal Definition of MI. We propose a more inclusive taxonomy that could serve as a framework for understanding biological disease mechanisms, therapeutic efficacy, and prognosis in this population.

Corrected flow time: a noninvasive ultrasound measure to detect preload reduction by nitroglycerin.

OBJECTIVE: Monitoring of patient's intravascular volume status without invasive measures remains challenging and unreliable. Our objective was to determine if corrected flow time (FTc) measurement could detect preload reduction with administration of nitroglycerin (NTG) as a surrogate for volume loss. METHODS: Post hoc FTc analysis was performed for a prospective cohort study of pulsed wave spectral Doppler measurements before and after administration of NTG. Patients enrolled were eligible for inclusion if they were admitted to a chest pain center for cardiac evaluation. Descriptive statistics, t tests, bivariate regression, and intraclass correlation coefficient were performed as appropriate. RESULTS: Fifty-four patients had Doppler measurements available for review. Mean FTc decreased from 339 milliseconds (95% confidence interval, 332-346) to 325 milliseconds (95% confidence interval, 318-331) with administration of 0.3 mg of sublingual NTG (P=.0001). Mean heart rate increased 5 beats/min with administration of NTG (P<.0001); however, there was no significant change in systolic or diastolic blood pressure. CONCLUSION: Corrected flow time was able to detect a significant difference in preload reduction with 0.3 mg of NTG. The FTc may be an early reliable noninvasive measure to detect changes in intravascular volume status.

Women and Chest Pain: Recognizing the Different Faces of Angina in the Emergency Department.

Emergency departments (ED) in the United States see over eight million cases of chest pain annually. While a cardinal symptom of acute coronary syndrome (ACS), multiple emergent and non-emergent causes can attribute to chest pain. This case-based perspective describes the different sex-specific causes of angina seen in ED patients. Once coronary artery disease (CAD) is ruled out with standard protocols, microvascular dysfunction is perhaps the most prevalent but under-diagnosed cause of non-CAD related angina in ED patients. Additional causes include coronary artery spasm, coronary artery dissection, coronary artery endothelial dysfunction and myocardial bridging. Non-CAD related angina is associated with persistent chest pain causing poor function, quality of life, and recidivism. Clinicians should consider additional diagnostics to routinely screen for non-CAD related causes of angina in patients with recurrent chest pain. Future work is needed to better define the epidemiological, clinical, biological, and genetic correlates of microvascular dysfunction in these patients.

Chest pain syndromes are associated with high rates of recidivism and costs in young United States Veterans.

BACKGROUND: Recurrent chest pain is common in patients with and without coronary artery disease. The prevalence and burden of these symptoms on healthcare is unknown. OBJECTIVES: To compare chest pain return visits (recidivism) in patients with unexplained chest pain (UCP) against reference group of patients with coronary artery disease (CAD) and estimate the annual cost of recurrent chest pain. METHODS: In a retrospective cohort study, a Veteran Affairs (VA) administrative and clinical database of Veterans who were deployed to or served in support of the wars in Iraq or Afghanistan was queried for first disease specific ICD-9 code to form two cohorts (UCP or CAD). Patients were followed between 09/2001-09/2010 for the first and cumulative return visits for UCP or cardiac pain (ACS or angina) to clinic, emergency department or admission; or for all-cause death. Time to return was analyzed using Cox regression and negative binomial models and adjusted for age, gender, race, marital status, and risk factors (hypertension, hyperlipidemia, diabetes, smoking and obesity). Direct total costs included inpatient, outpatient and fee basis (non-VA) costs. RESULTS: Of 749,036 patients, 20,521 had UCP and 5303 had CAD. UCP patients were young and had a lower burden of risk factors than CAD cohort (p < .01). Yet, these patients were likely to return earlier with any chest pain (adjusted Hazard Ratio [aHR] = 1.76; 95 % CI 1.65-1.88); or unexplained chest pain than CAD patients (aHR: 1.89; 95 % CI 1.77-2.01). UCP patients were also likely to return more frequently for any chest pain (aRate Ratio = 1.54; 95 % CI 1.43-1.64) or UCP than CAD patients (aRR =2.63; 95 % CI 2.43-2.87). Per 100 patients, the 1-year cumulative returns were 37 visits for reference group and 45 visits for UCP cohort. The annual costs for chest pain averaged $69,009 for CAD and $57,336 for UCP patients (log geometric mean ratio=1.25; 95 % CI 1.18-1.32). CONCLUSION: Chest pain recidivism is common and costly even in patients without known CAD. We need evidence-based guidelines for these patients to minimize returns.

Effectiveness of Updated 2023-2024 (Monovalent XBB.1.5) COVID-19 Vaccination Against SARS-CoV-2 Omicron XBB and BA.2.86/JN.1 Lineage Hospitalization and a Comparison of Clinical Severity - IVY Network, 26 Hospitals, October 18, 2023-March 9, 2024.

Background: Assessing COVID-19 vaccine effectiveness (VE) and severity of SARS-CoV-2 variants can inform public health risk assessments and decisions about vaccine composition. BA.2.86 and its descendants, including JN.1 (referred to collectively as "JN lineages"), emerged in late 2023 and exhibited substantial genomic divergence from co-circulating XBB lineages. Methods: We analyzed patients hospitalized with COVID-19-like illness at 26 hospitals in 20 U.S. states admitted October 18, 2023-March 9, 2024. Using a test-negative, case-control design, we estimated the effectiveness of an updated 2023-2024 (Monovalent XBB.1.5) COVID-19 vaccine dose against sequence-confirmed XBB and JN lineage hospitalization using logistic regression. Odds of severe outcomes, including intensive care unit (ICU) admission and invasive mechanical ventilation (IMV) or death, were compared for JN versus XBB lineage hospitalizations using logistic regression. Results: 585 case-patients with XBB lineages, 397 case-patients with JN lineages, and 4,580 control-patients were included. VE in the first 7-89 days after receipt of an updated dose was 54.2% (95% CI = 36.1%-67.1%) against XBB lineage hospitalization and 32.7% (95% CI = 1.9%-53.8%) against JN lineage hospitalization. Odds of ICU admission (adjusted odds ratio [aOR] 0.80; 95% CI = 0.46-1.38) and IMV or death (aOR 0.69; 95% CI = 0.34-1.40) were not significantly different among JN compared to XBB lineage hospitalizations. Conclusions: Updated 2023-2024 COVID-19 vaccination provided protection against both XBB and JN lineage hospitalization, but protection against the latter may be attenuated by immune escape. Clinical severity of JN lineage hospitalizations was not higher relative to XBB lineage hospitalizations.

Severity of Respiratory Syncytial Virus vs COVID-19 and Influenza Among Hospitalized US Adults.

Importance: On June 21, 2023, the Centers for Disease Control and Prevention recommended the first respiratory syncytial virus (RSV) vaccines for adults aged 60 years and older using shared clinical decision-making. Understanding the severity of RSV disease in adults can help guide this clinical decision-making. Objective: To describe disease severity among adults hospitalized with RSV and compare it with the severity of COVID-19 and influenza disease by vaccination status. Design, Setting, and Participants: In this cohort study, adults aged 18 years and older admitted to the hospital with acute respiratory illness and laboratory-confirmed RSV, SARS-CoV-2, or influenza infection were prospectively enrolled from 25 hospitals in 20 US states from February 1, 2022, to May 31, 2023. Clinical data during each patient's hospitalization were collected using standardized forms. Data were analyzed from August to October 2023. Exposures: RSV, SARS-CoV-2, or influenza infection. Main Outcomes and Measures: Using multivariable logistic regression, severity of RSV disease was compared with COVID-19 and influenza severity, by COVID-19 and influenza vaccination status, for a range of clinical outcomes, including the composite of invasive mechanical ventilation (IMV) and in-hospital death. Results: Of 7998 adults (median [IQR] age, 67 [54-78] years; 4047 [50.6%] female) included, 484 (6.1%) were hospitalized with RSV, 6422 (80.3%) were hospitalized with COVID-19, and 1092 (13.7%) were hospitalized with influenza. Among patients with RSV, 58 (12.0%) experienced IMV or death, compared with 201 of 1422 unvaccinated patients with COVID-19 (14.1%) and 458 of 5000 vaccinated patients with COVID-19 (9.2%), as well as 72 of 699 unvaccinated patients with influenza (10.3%) and 20 of 393 vaccinated patients with influenza (5.1%). In adjusted analyses, the odds of IMV or in-hospital death were not significantly different among patients hospitalized with RSV and unvaccinated patients hospitalized with COVID-19 (adjusted odds ratio [aOR], 0.82; 95% CI, 0.59-1.13; P = .22) or influenza (aOR, 1.20; 95% CI, 0.82-1.76; P = .35); however, the odds of IMV or death were significantly higher among patients hospitalized with RSV compared with vaccinated patients hospitalized with COVID-19 (aOR, 1.38; 95% CI, 1.02-1.86; P = .03) or influenza disease (aOR, 2.81; 95% CI, 1.62-4.86; P < .001). Conclusions and Relevance: Among adults hospitalized in this US cohort during the 16 months before the first RSV vaccine recommendations, RSV disease was less common but similar in severity compared with COVID-19 or influenza disease among unvaccinated patients and more severe than COVID-19 or influenza disease among vaccinated patients for the most serious outcomes of IMV or death.