Impact of COVID-19 Pandemic on Sex and Racial Disparities in Chest Pain Presentation and Management Through the Emergency Department.

Background: Sex and racial disparities in the presentation and management of chest pain persist, however, the impact of coronavirus disease 2019 (COVID-19) on these disparities have not been studied. We sought to determine whether the COVID-19 pandemic contributed to pre-existing sex and racial disparities in the presentation, management, and outcomes of patients presenting to the emergency department (ED) with chest pain. Methods: We conducted an observational cohort study with retrospective data collection of patients between January 1, 2016, and May 1, 2022. This was a single study conducted at a quaternary academic medical center of all patients who presented to the ED with a complaint of chest pain or chest pain equivalent symptoms. Patient were further segregated into different groups based on sex (male, female), race, ethnicity (Asian, Black, Hispanic, White, and other), and age (18 - 40, 41 - 65, > 65). We compared diagnostic evaluations, treatment decisions, and outcomes during prespecified time points before, during, and after the COVID-19 pandemic. Results: This study included 95,764 chest pain encounters. Total chest pain presentations to the ED fell about 38% during the early pandemic months. Females presented significantly less than males during initial COVID-19 (48% vs. 52%, P < 0.001) and Asian females were least likely to present. There was an increase in the total number of troponins and echocardiograms ordered during peak COVID-19 across both sexes, but females were still less likely to have these tests ordered across all timepoints. The number of coronary angiograms did not increase during peak COVID-19, and females were less likely to undergo coronary angiogram during all timepoints. Finally, females with chest pain were less likely to be diagnosed with acute myocardial infarction (AMI) during all timepoints, while in-hospital deaths were similar between males and females during all timepoints. Conclusions: During COVID-19, females, especially Asian females, were less likely to present to the ED for chest pain. Non-White patients were less likely to present to the ED compared to White patients prior to and during the pandemic. Disparities in management and outcomes of chest pain encounters remained similar to pre-COVID-19, with females receiving less cardiac workup and AMI diagnoses than males, but in-hospital mortality remaining similar between groups and timepoints.

Mitral Regurgitation in Female Patients: Sex Differences and Disparities.

Mitral regurgitation is the most common valvular disease, particularly in older adults. Recent literature has consistently supported that there are significant differences in mitral regurgitation outcomes between male and female patients and that this is likely multifactorial. Numerous sex differences in anatomy and pathophysiology may play a role in delayed diagnoses, referrals, and treatments for female patients. Despite the recognition of these discrepancies in the literature, many guidelines that steer clinical care do not incorporate these factors into society recommendations. Identifying and validating sex-specific diagnostic parameters and increasing the representation of female patients in trials of new mitral regurgitation treatment modalities are key factors in improving outcomes for female patients.

Echocardiographic Predictors of Suboptimal Transcatheter Mitral Valve Repair in Patients With Secondary Mitral Regurgitation.

Background: Residual mitral regurgitation (MR) following mitral valve transcatheter edge-to-edge repair (TEER) is associated with worse outcomes. This study sought to identify echocardiographic predictors of suboptimal residual MR after TEER in patients with secondary MR. Methods: In this retrospective single-center study, we identified all patients with secondary MR who underwent TEER between 2016 and 2021. Pre- and intraprocedural transesophageal echocardiographic images were reviewed. The primary outcome was suboptimal residual MR, defined as ≥2+ residual MR on postprocedural transesophageal echocardiography. The association of preprocedural echocardiographic parameters with the primary outcome was tested via logistic regression. Results: Sixty-five patients (69 ± 15 years; 49% women) with secondary MR underwent TEER with MitraClip. All patients had moderate-severe or severe (3-4+) MR preoperatively, with an average left ventricular ejection fraction of 35% and New York Heart Association class III symptoms. Procedural success, defined as ≤2+ MR post-TEER, was achieved in 94%. A suboptimal residual MR was observed in 38%. Independent predictors of suboptimal residual MR included bicommissural MR (odds ratio [OR], 7.95; 95% CI, 1.50-42.3; P = .02), 2-dimensional anteroposterior diameter (OR, 6.46; 95% CI, 1.85-22.51 per cm; P < .01), and mitral valve area to left ventricular end-diastolic volume ratio (OR, 0.69; 95% CI, 0.50-0.93 per mm2/mL; P = .02). Conclusions: Certain echocardiographic features, including bicommissural MR, a larger annular diameter, and a smaller ratio of mitral valve area to left ventricular end-diastolic volume, are associated with suboptimal residual MR following TEER. These preprocedural measurements may optimize patient selection in those with secondary MR being considered for TEER.

Impact of frailty on short term outcomes, resource use, and readmissions after transcatheter mitral valve repair: A national analysis.

BACKGROUND: Treatment options for mitral regurgitation range from diuretic therapy, to surgical and interventional strategies including TMVR in high-risk surgical candidates. Frailty has been associated with inferior outcomes following hospitalizations for heart failure and in open cardiac surgery. OBJECTIVE: The purpose of the present study was to evaluate the impact of frailty on clinical outcomes and resource use following transcatheter mitral valve repair (TMVR). METHODS: Adults undergoing TMVR were identified using the 2016-2018 Nationwide Readmissions Database, and divided into Frail and Non-Frail groups. Frailty was defined using a derivative of the Johns Hopkins Adjusted Clinical Groups frailty indicator. Generalized linear models were used to assess the association of frailty with in-hospital mortality, complications, nonhome discharge, hospitalization costs, length of stay, and non-elective readmission at 90 days. Average marginal effects were used to quantify the impact of frailty on predicted mortality. RESULTS: Of 18,791 patients undergoing TMVR, 11.6% were considered frail. The observed mortality rate for the overall cohort was 2.2%. After adjustment, frailty was associated with increased odds of in-hospital mortality (AOR 1.8, 95% CI 1.2-2.6), corresponding to an absolute increase in risk of mortality of 1.1%. Frailty was associated with a 2.7-day (95% CI 2.1-3.2) increase in postoperative LOS, and $18,300 (95% CI 14,400-22,200) increment in hospitalization costs. Frail patients had greater odds (4.4, 95% CI 3.6-5.4) of nonhome discharge but similar odds of non-elective 90-day readmission. CONCLUSIONS: Frailty is independently associated with inferior short-term clinical outcomes and greater resource use following TMVR. Inclusion of frailty into existing risk models may better inform choice of therapy and shared decision-making.

Sex Differences in the Association of Body Composition and Cardiovascular Mortality.

Background To determine whether differences in body composition contribute to sex differences in cardiovascular disease (CVD) mortality, we investigated the relationship between components of body composition and CVD mortality in healthy men and women. Methods and Results Dual energy x-ray absorptiometry body composition data from the National Health and Nutrition Examination Survey 1999-2004 and CVD mortality data from the National Health and Nutrition Examination Survey 1999-2014 were evaluated in 11 463 individuals 20 years of age and older. Individuals were divided into 4 body composition groups (low muscle mass-low fat mass-the referent; low muscle-high fat; high muscle-low fat, and high muscle-high fat), and adjusted competing risks analyses were performed for CVD versus non-CVD mortality. In women, high muscle/high fat mass was associated with a significantly lower adjusted CVD mortality rate (hazard ratio [HR], 0.58; 95% CI, 0.39-0.86; P=0.01), but high muscle/low fat mass was not. In men, both high muscle-high fat (HR, 0.74; 95% CI, 0.53-1.04; P=0.08) and high muscle-low fat mass (HR, 0.40; 95% CI, 0.21-0.77; P=0.01) were associated with lower CVD. Further, in adjusted competing risks analyses stratified by sex, the CVD rate in women tends to significantly decrease as normalized total fat increase (total fat fourth quartile: HR, 0.56; 95% CI, 0.34-0.94; P<0.03), whereas this is not noted in men. Conclusions Higher muscle mass is associated with lower CVD and mortality in men and women. However, in women, high fat, regardless of muscle mass level, appears to be associated with lower CVD mortality risk. This finding highlights the importance of muscle mass in healthy men and women for CVD risk prevention, while suggesting sexual dimorphism with respect to the CVD risk associated with fat mass.

Women in Cardiology Twitter Network: An Analysis of a Global Professional Virtual Community From 2016 to 2019.

Background Social media is an effective channel for the advancement of women physicians; however, its use by women in cardiology has not been systematically studied. Our study seeks to characterize the current Women in Cardiology Twitter network. Methods and Results Six women-specific cardiology Twitter hashtags were analyzed: #ACCWIC (American College of Cardiology Women in Cardiology), #AHAWIC (American Heart Association Women in Cardiology), #ilooklikeacardiologist, #SCAIWIN (Society for Cardiovascular Angiography and Interventions Women in Innovations), #WomeninCardiology, and #WomeninEP (Women in Electrophysiology). Twitter data from 2016 to 2019 were obtained from Symplur Signals. Quantitative and descriptive content analyses were performed. The Women in Cardiology Twitter network generated 48 236 tweets, 266 180 903 impressions, and 12 485 users. Tweets increased by 706% (from 2083 to 16 780), impressions by 207% (from 26 755 476 to 82 080 472), and users by 440% (from 796 to 4300), including a 471% user increase internationally. The network generated 6530 (13%) original tweets and 43 103 (86%) amplification tweets. Most original and amplification tweets were authored by women (81% and 62%, respectively) and women physicians (76% and 52%, respectively), with an increase in original and amplification tweets authored by academic women physicians (98% and 109%, respectively) and trainees (390% and 249%, respectively) over time. Community building, professional development, and gender advocacy were the most common tweet contents over the study period. Community building was the most common tweet category for #ACCWIC, #AHAWIC, #ilooklikeacardiologist, #SCAIWIN, and #WomeninCardiology, whereas professional development was most common for #WomeninEP. Conclusions The Women in Cardiology Twitter network has grown immensely from 2016 to 2019, with women physicians as the driving contributors. This network has become an important channel for community building, professional development, and gender advocacy discussions in an effort to advance women in cardiology.

Sudden Cardiac Arrest in a Patient With Myxedema Coma and COVID-19.

SARS-CoV-2 infection is associated with significant lung and cardiac morbidity but there is a limited understanding of the endocrine manifestations of coronavirus disease 2019 (COVID-19). Although thyrotoxicosis due to subacute thyroiditis has been reported in COVID-19, it is unknown whether SARS-CoV-2 infection can also lead to decompensated hypothyroidism. We present the first case of myxedema coma (MC) in COVID-19 and we discuss how SARS-CoV-2 may have precipitated multiorgan damage and sudden cardiac arrest in our patient. A 69-year-old woman with a history of small cell lung cancer presented with hypothermia, hypotension, decreased respiratory rate, and a Glasgow Coma Scale score of 5. The patient was intubated and administered vasopressors. Laboratory investigation showed elevated thyrotropin, very low free thyroxine, elevated thyroid peroxidase antibody, and markedly elevated inflammatory markers. SARS-CoV-2 test was positive. Computed tomography showed pulmonary embolism and peripheral ground-glass opacities in the lungs. The patient was diagnosed with myxedema coma with concomitant COVID-19. While treatment with intravenous hydrocortisone and levothyroxine were begun the patient developed a junctional escape rhythm. Eight minutes later, the patient became pulseless and was eventually resuscitated. Echocardiogram following the arrest showed evidence of right heart dysfunction. She died 2 days later of multiorgan failure. This is the first report of SARS-CoV-2 infection with MC. Sudden cardiac arrest likely resulted from the presence of viral pneumonia, cardiac arrhythmia, pulmonary emboli, and MC-all of which were associated with the patient's SARS-CoV-2 infection.

Angiotensin Converting Enzyme Inhibitor and Angiotensin II Receptor Blocker Use Among Outpatients Diagnosed With COVID-19.

Coronavirus disease 2019 (COVID-19) is a viral pandemic precipitated by the severe acute respiratory syndrome coronavirus 2. Since previous reports suggested that viral entry into cells may involve angiotensin converting enzyme 2, there has been growing concern that angiotensin converting enzyme inhibitor (ACEI) and angiotensin II receptor blocker (ARB) use may exacerbate the disease severity. In this retrospective, single-center US study of adult patients diagnosed with COVID-19, we evaluated the association of ACEI/ARB use with hospital admission. Secondary outcomes included: ICU admission, mechanical ventilation, length of hospital stay, use of inotropes, and all-cause mortality. Propensity score matching was performed to account for potential confounders. Among 590 unmatched patients diagnosed with COVID-19, 78 patients were receiving ACEI/ARB (median age 63 years and 59.7% male) and 512 patients were non-users (median age 42 years and 47.1% male). In the propensity matched population, multivariate logistic regression analysis adjusting for age, gender and comorbidities demonstrated that ACEI/ARB use was not associated with hospital admission (OR 1.2, 95%CI 0.5 to 2.7, p = 0.652). CAD and CKD/end stage renal disease [ESRD] remained independently associated with admission to hospital. All-cause mortality, ICU stay, need for ventilation, and inotrope use was not significantly different between the 2 study groups. In conclusion, among patients who were diagnosed with COVID-19, ACEI/ARB use was not associated with increased risk of hospital admission.

Percutaneous edge-to-edge repair for common atrioventricular valve regurgitation in a patient with heterotaxy syndrome, single ventricle physiology, and unbalanced atrioventricular septal defect.

Congenital heart disease patients, specifically with unbalanced atrioventricular septal defects and common atrioventricular valves requiring single ventricle palliation, have substantial morbidity and mortality. Atrioventricular valve regurgitation (AVVR) is associated with poor outcomes in single ventricle patients, and many of them require surgical treatment of AVVR in their lifetimes. We describe a unique case of transcatheter edge-to-edge valve repair using the MitraClip system (Abbott, Chicago, IL) in a single ventricle patient with severe common AVVR.

In-Hospital ST-Segment Elevation Myocardial Infarction: Improving Diagnosis, Triage, and Treatment.

Importance: In-hospital ST-segment elevation myocardial infarction (STEMI) is a unique clinical entity with epidemiology, incidence, and outcomes distinct from that of out-of-hospital STEMI and has only within the past 10 years begun to receive increased attention and research. Patients with in-hospital STEMI are older, have more comorbidities, and more frequently have coagulopathies and contraindications for anticoagulation and fibrinolytic therapy. A standardized clinical definition of in-hospital STEMI is lacking. The objectives of this special communication are to (1) summarize the knowledge base regarding in-hospital STEMI; (2) review the challenges of diagnosis and treatment of patients with in-hospital STEMI; (3) present a standardized clinical definition for in-hospital STEMI; and (4) provide a quality improvement protocol to improve diagnosis, triage, and treatment of patients with in-hospital STEMI. Observations: Patients with in-hospital STEMI less frequently present with typical angina symptoms, and an electrocardiogram is often obtained owing to changes in clinical status, changes on telemetry, or a finding of elevated cardiac biomarker. The frequent nontypical presentations often lead to substantial delays in the diagnosis of STEMI. Only 34% to 71% of patients with in-hospital STEMI undergo diagnostic catheterization, and only 22% to 56% undergo percutaneous coronary intervention. Even in contemporary reports, some studies report in-hospital mortality in the range of 31% to 42%. Three areas of delay in the treatment of patients with in-hospital STEMI that merit particular attention are (1) delays in electrocardiogram acquisition, (2) delays in electrocardiogram interpretation, and (3) delays in activation of existing STEMI systems of care. Conclusions and Relevance: Treatment of patients with in-hospital STEMI is more complex and challenging than treatment of patients who develop out-of-hospital STEMI, leading to delays in diagnosis and triage and less frequent use of reperfusion therapy. Quality improvement programs targeted at decreasing delays and streamlining treatment of such patients may improve treatment and outcome.

Everolimus-eluting stents stabilize plaque inflammation in vivo: assessment by intravascular fluorescence molecular imaging.

AIMS: Inflammation drives atherosclerosis complications and is a promising therapeutic target for plaque stabilization. At present, it is unknown whether local stenting approaches can stabilize plaque inflammation in vivo. Here, we investigate whether everolimus-eluting stents (EES) can locally suppress plaque inflammatory protease activity in vivo using intravascular near-infrared fluorescence (NIRF) molecular imaging. METHODS AND RESULTS: Balloon-injured, hyperlipidaemic rabbits with atherosclerosis received non-overlapping EES and bare metal stents (BMS) placement into the infrarenal aorta (n = 7 EES, n = 7 BMS, 3.5 mm diameter x 12 mm length). Four weeks later, rabbits received an injection of the cysteine protease-activatable NIRF imaging agent Prosense VM110. Twenty-four hours later, co-registered intravascular 2D NIRF, X-ray angiography and intravascular ultrasound imaging were performed. In vivo EES-stented plaques contained substantially reduced NIRF inflammatory protease activity compared with untreated plaques and BMS-stented plaques (P = 0.006). Ex vivo macroscopic NIRF imaging of plaque protease activity corroborated the in vivo results (P = 0.003). Histopathology analyses revealed that EES-treated plaques showed reduced neointimal and medial arterial macrophage and cathepsin B expression compared with unstented and BMS-treated plaques. CONCLUSIONS: EES-stenting stabilizes plaque inflammation as assessed by translational intravascular NIRF molecular imaging in vivo. These data further support that EES may provide a local approach for stabilizing inflamed plaques.

Targeted Near-Infrared Fluorescence Imaging of Atherosclerosis: Clinical and Intracoronary Evaluation of Indocyanine Green.

OBJECTIVES: This study sought to determine whether indocyanine green (ICG)-enhanced near-infrared fluorescence (NIRF) imaging can illuminate high-risk histologic plaque features of human carotid atherosclerosis, and in coronary atheroma of living swine, using intravascular NIRF-optical coherence tomography (OCT) imaging. BACKGROUND: New translatable imaging approaches are needed to identify high-risk biological signatures of atheroma. ICG is a U.S. Food and Drug Administration-approved NIRF imaging agent that experimentally targets plaque macrophages and lipid in areas of enhanced endothelial permeability. However, it is unknown whether ICG can target atheroma in patients. METHODS: Eight patients were enrolled in the BRIGHT-CEA (Indocyanine Green Fluorescence Uptake in Human Carotid Artery Plaque) trial. Five patients were injected intravenously with ICG 99 ± 25 min before clinically indicated carotid endarterectomy. Three saline-injected endarterectomy patients served as control subjects. Excised plaques underwent analysis by intravascular NIRF-OCT, reflectance imaging, microscopy, and histopathology. Next, following ICG intravenous injection, in vivo intracoronary NIRF-OCT and intravascular ultrasound imaged 3 atheroma-bearing coronary arteries of a diabetic, cholesterol-fed swine. RESULTS: ICG was well tolerated; no adverse clinical events occurred up to 30 days post-injection. Multimodal NIRF imaging including intravascular NIRF-OCT revealed that ICG accumulated in all endarterectomy specimens. Plaques from saline-injected control patients exhibited minimal NIRF signal. In the swine experiment, intracoronary NIRF-OCT identified ICG uptake in all intravascular ultrasound-identified plaques in vivo. On detailed microscopic evaluation, ICG localized to plaque areas exhibiting impaired endothelial integrity, including disrupted fibrous caps, and within areas of neovascularization. Within human plaque areas of endothelial abnormality, ICG was spatially related to localized zones of plaque macrophages and lipid, and, notably, intraplaque hemorrhage. CONCLUSIONS: This study demonstrates that ICG targets human plaques exhibiting endothelial abnormalities and provides new insights into its targeting mechanisms in clinical and experimental atheroma. Intracoronary NIRF-OCT of ICG may offer a novel, clinically translatable approach to image pathobiological aspects of coronary atherosclerosis. (Indocyanine Green Fluorescence Uptake in Human Carotid Artery Plaque [BRIGHT-CEA]; NCT01873716).