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Development and external validation of a dynamic risk score for early prediction of cardiogenic shock in cardiac intensive care units using machine learning

Hu, Yuxuan; Lui, Albert; Goldstein, Mark; Sudarshan, Mukund; Tinsay, Andrea; Tsui, Cindy; Maidman, Samuel D; Medamana, John; Jethani, Neil; Puli, Aahlad; Nguy, Vuthy; Aphinyanaphongs, Yindalon; Kiefer, Nicholas; Smilowitz, Nathaniel R; Horowitz, James; Ahuja, Tania; Fishman, Glenn I; Hochman, Judith; Katz, Stuart; Bernard, Samuel; Ranganath, Rajesh
BACKGROUND:Myocardial infarction and heart failure are major cardiovascular diseases that affect millions of people in the US with the morbidity and mortality being highest among patients who develop cardiogenic shock. Early recognition of cardiogenic shock allows prompt implementation of treatment measures. Our objective is to develop a new dynamic risk score, called CShock, to improve early detection of cardiogenic shock in cardiac intensive care unit (ICU). METHODS:We developed and externally validated a deep learning-based risk stratification tool, called CShock, for patients admitted into the cardiac ICU with acute decompensated heart failure and/or myocardial infarction to predict onset of cardiogenic shock. We prepared a cardiac ICU dataset using MIMIC-III database by annotating with physician adjudicated outcomes. This dataset that consisted of 1500 patients with 204 having cardiogenic/mixed shock was then used to train CShock. The features used to train the model for CShock included patient demographics, cardiac ICU admission diagnoses, routinely measured laboratory values and vital signs, and relevant features manually extracted from echocardiogram and left heart catheterization reports. We externally validated the risk model on the New York University (NYU) Langone Health cardiac ICU database that was also annotated with physician adjudicated outcomes. The external validation cohort consisted of 131 patients with 25 patients experiencing cardiogenic/mixed shock. RESULTS:CShock achieved an area under the receiver operator characteristic curve (AUROC) of 0.821 (95% CI 0.792-0.850). CShock was externally validated in the more contemporary NYU cohort and achieved an AUROC of 0.800 (95% CI 0.717-0.884), demonstrating its generalizability in other cardiac ICUs. Having an elevated heart rate is most predictive of cardiogenic shock development based on Shapley values. The other top ten predictors are having an admission diagnosis of myocardial infarction with ST-segment elevation, having an admission diagnosis of acute decompensated heart failure, Braden Scale, Glasgow Coma Scale, Blood urea nitrogen, Systolic blood pressure, Serum chloride, Serum sodium, and Arterial blood pH. CONCLUSIONS:The novel CShock score has the potential to provide automated detection and early warning for cardiogenic shock and improve the outcomes for the millions of patients who suffer from myocardial infarction and heart failure.
PMID: 38518758
ISSN: 2048-8734
CID: 5640892

Implementing a Clinical Decision Support Tool to Improve Physical Activity

McCarthy, Margaret M; Szerencsy, Adam; Taza-Rocano, Leslie; Hopkins, Stephanie; Mann, Devin; D'Eramo Melkus, Gail; Vorderstrasse, Allison; Katz, Stuart D
BACKGROUND:Currently, only about half of U.S. adults achieve current physical activity guidelines. Routine physical activity is not regularly assessed, nor are patients routinely counseled by their health care provider on achieving recommended levels. The three-question physical activity vital sign (PAVS) was developed to assess physical activity duration and intensity and identify adults not meeting physical activity guidelines. Clinical decision support provided via a best practice advisory in an electronic health record (EHR) system can be triggered as a prompt, reminding health care providers to implement the best practice intervention when appropriate. Remote patient monitoring of physical activity can provide objective data in the EHR. OBJECTIVES/OBJECTIVE:This study aimed to evaluate the feasibility and clinical utility of embedding the PAVS and a triggered best practice advisor into the EHR in an ambulatory preventive cardiology practice setting to alert providers to patients reporting low physical activity and prompt health care providers to counsel these patients as needed. METHODS:Three components based in the EHR were integrated for the purpose of this study: patients completed the PAVS through their electronic patient portal prior to an office visit; a best practice advisory was created to prompt providers to counsel patients who reported low levels of physical activity; and remote patient monitoring via Fitbit synced to the EHR provided objective physical activity data. The intervention was pilot-tested in the Epic EHR for 1 year (July 1, 2021-June 30, 2022). Qualitative feedback on the intervention from both providers and patients was obtained at the completion of the study. RESULTS:Monthly assessments of the use of the PAVS and best practice advisory and remote patient monitoring were completed. Patients' completion of the PAVS varied from 35% to 48% per month. The best practice advisory was signed by providers between 2% and 65% and was acknowledged by 2% to 22% per month. The majority (58%) of patients were able to sync a Fitbit device to their EHR for remote monitoring. DISCUSSION/CONCLUSIONS:Although uptake of each component needs improvement, this pilot demonstrated the feasibility of incorporating a PA promotion intervention into the EHR. Qualitative feedback provided guidance for future implementation.
PMID: 38207172
ISSN: 1538-9847
CID: 5631332

Researching COVID to enhance recovery (RECOVER) tissue pathology study protocol: Rationale, objectives, and design

Troxel, Andrea B; Bind, Marie-Abele C; Flotte, Thomas J; Cordon-Cardo, Carlos; Decker, Lauren A; Finn, Aloke V; Padera, Robert F; Reichard, R Ross; Stone, James R; Adolphi, Natalie L; Casimero, Faye Victoria C; Crary, John F; Elifritz, Jamie; Faustin, Arline; Ghosh, Saikat Kumar B; Krausert, Amanda; Martinez-Lage, Maria; Melamed, Jonathan; Mitchell, Roger A; Sampson, Barbara A; Seifert, Alan C; Simsir, Aylin; Adams, Cheryle; Haasnoot, Stephanie; Hafner, Stephanie; Siciliano, Michelle A; Vallejos, Brittany B; Del Boccio, Phoebe; Lamendola-Essel, Michelle F; Young, Chloe E; Kewlani, Deepshikha; Akinbo, Precious A; Parent, Brendan; Chung, Alicia; Cato, Teresa C; Mudumbi, Praveen C; Esquenazi-Karonika, Shari; Wood, Marion J; Chan, James; Monteiro, Jonathan; Shinnick, Daniel J; Thaweethai, Tanayott; Nguyen, Amber N; Fitzgerald, Megan L; Perlowski, Alice A; Stiles, Lauren E; Paskett, Moira L; Katz, Stuart D; Foulkes, Andrea S; ,
IMPORTANCE/OBJECTIVE:SARS-CoV-2 infection can result in ongoing, relapsing, or new symptoms or organ dysfunction after the acute phase of infection, termed Post-Acute Sequelae of SARS-CoV-2 (PASC), or long COVID. The characteristics, prevalence, trajectory and mechanisms of PASC are poorly understood. The objectives of the Researching COVID to Enhance Recovery (RECOVER) tissue pathology study (RECOVER-Pathology) are to: (1) characterize prevalence and types of organ injury/disease and pathology occurring with PASC; (2) characterize the association of pathologic findings with clinical and other characteristics; (3) define the pathophysiology and mechanisms of PASC, and possible mediation via viral persistence; and (4) establish a post-mortem tissue biobank and post-mortem brain imaging biorepository. METHODS:RECOVER-Pathology is a cross-sectional study of decedents dying at least 15 days following initial SARS-CoV-2 infection. Eligible decedents must meet WHO criteria for suspected, probable, or confirmed infection and must be aged 18 years or more at the time of death. Enrollment occurs at 7 sites in four U.S. states and Washington, DC. Comprehensive autopsies are conducted according to a standardized protocol within 24 hours of death; tissue samples are sent to the PASC Biorepository for later analyses. Data on clinical history are collected from the medical records and/or next of kin. The primary study outcomes include an array of pathologic features organized by organ system. Causal inference methods will be employed to investigate associations between risk factors and pathologic outcomes. DISCUSSION/CONCLUSIONS:RECOVER-Pathology is the largest autopsy study addressing PASC among US adults. Results of this study are intended to elucidate mechanisms of organ injury and disease and enhance our understanding of the pathophysiology of PASC.
PMID: 38198481
ISSN: 1932-6203
CID: 5628642

Impact of Visit Volume on the Effectiveness of Electronic Tools to Improve Heart Failure Care

Mukhopadhyay, Amrita; Reynolds, Harmony R; King, William C; Phillips, Lawrence M; Nagler, Arielle R; Szerencsy, Adam; Saxena, Archana; Klapheke, Nathan; Katz, Stuart D; Horwitz, Leora I; Blecker, Saul
BACKGROUND:Electronic health record (EHR) tools can improve prescribing of guideline-recommended therapies for heart failure with reduced ejection fraction (HFrEF), but their effectiveness may vary by physician workload. OBJECTIVES/OBJECTIVE:This paper aims to assess whether physician workload modifies the effectiveness of EHR tools for HFrEF. METHODS:This was a prespecified subgroup analysis of the BETTER CARE-HF (Building Electronic Tools to Enhance and Reinforce Cardiovascular Recommendations for Heart Failure) cluster-randomized trial, which compared effectiveness of an alert vs message vs usual care on prescribing of mineralocorticoid antagonists (MRAs). The trial included adults with HFrEF seen in cardiology offices who were eligible for and not prescribed MRAs. Visit volume was defined at the cardiologist-level as number of visits per 6-month study period (high = upper tertile vs non-high = remaining). Analysis at the patient-level used likelihood ratio test for interaction with log-binomial models. RESULTS:Among 2,211 patients seen by 174 cardiologists, 932 (42.2%) were seen by high-volume cardiologists (median: 1,853; Q1-Q3: 1,637-2,225 visits/6 mo; and median: 10; Q1-Q3: 9-12 visits/half-day). MRA was prescribed to 5.5% in the high-volume vs 14.8% in the non-high-volume groups in the usual care arm, 10.3% vs 19.6% in the message arm, and 31.2% vs 28.2% in the alert arm, respectively. Visit volume modified treatment effect (P for interaction = 0.02) such that the alert was more effective in the high-volume group (relative risk: 5.16; 95% CI: 2.57-10.4) than the non-high-volume group (relative risk: 1.93; 95% CI: 1.29-2.90). CONCLUSIONS:An EHR-embedded alert increased prescribing by >5-fold among patients seen by high-volume cardiologists. Our findings support use of EHR alerts, especially in busy practice settings. (Building Electronic Tools to Enhance and Reinforce Cardiovascular Recommendations for Heart Failure [BETTER CARE-HF]; NCT05275920).
PMID: 38043045
ISSN: 2213-1787
CID: 5597482

DIAPH1-MFN2 interaction regulates mitochondria-SR/ER contact and modulates ischemic/hypoxic stress

Yepuri, Gautham; Ramirez, Lisa M; Theophall, Gregory G; Reverdatto, Sergei V; Quadri, Nosirudeen; Hasan, Syed Nurul; Bu, Lei; Thiagarajan, Devi; Wilson, Robin; Díez, Raquel López; Gugger, Paul F; Mangar, Kaamashri; Narula, Navneet; Katz, Stuart D; Zhou, Boyan; Li, Huilin; Stotland, Aleksandr B; Gottlieb, Roberta A; Schmidt, Ann Marie; Shekhtman, Alexander; Ramasamy, Ravichandran
Inter-organelle contact and communication between mitochondria and sarco/endoplasmic reticulum (SR/ER) maintain cellular homeostasis and are profoundly disturbed during tissue ischemia. We tested the hypothesis that the formin Diaphanous-1 (DIAPH1), which regulates actin dynamics, signal transduction and metabolic functions, contributes to these processes. We demonstrate that DIAPH1 interacts directly with Mitofusin-2 (MFN2) to shorten mitochondria-SR/ER distance, thereby enhancing mitochondria-ER contact in cells including cardiomyocytes, endothelial cells and macrophages. Solution structure studies affirm the interaction between the Diaphanous Inhibitory Domain and the cytosolic GTPase domain of MFN2. In male rodent and human cardiomyocytes, DIAPH1-MFN2 interaction regulates mitochondrial turnover, mitophagy, and oxidative stress. Introduction of synthetic linker construct, which shorten the mitochondria-SR/ER distance, mitigated the molecular and functional benefits of DIAPH1 silencing in ischemia. This work establishes fundamental roles for DIAPH1-MFN2 interaction in the regulation of mitochondria-SR/ER contact networks. We propose that targeting pathways that regulate DIAPH1-MFN2 interactions may facilitate recovery from tissue ischemia.
PMID: 37903764
ISSN: 2041-1723
CID: 5610492

Rare Variant Genetics and Dilated Cardiomyopathy Severity: The DCM Precision Medicine Study

Hofmeyer, Mark; Haas, Garrie J; Jordan, Elizabeth; Cao, Jinwen; Kransdorf, Evan; Ewald, Gregory A; Morris, Alanna A; Owens, Anjali; Lowes, Brian; Stoller, Douglas; Wilson Tang, W H; Garg, Sonia; Trachtenberg, Barry H; Shah, Palak; Pamboukian, Salpy V; Sweitzer, Nancy K; Wheeler, Matthew T; Wilcox, Jane E; Katz, Stuart; Pan, Stephen; Jimenez, Javier; Smart, Frank; Wang, Jessica; Gottlieb, Stephen S; Judge, Daniel P; Moore, Charles K; Huggins, Gordon S; Kinnamon, Daniel D; Ni, Hanyu; Hershberger, Ray E; ,
BACKGROUND:Dilated cardiomyopathy (DCM) can lead to advanced disease, defined herein as necessitating a durable left ventricular assist device or a heart transplant (LVAD/HT). DCM is known to have a genetic basis, but the association of rare variant genetics with advanced DCM has not been studied. METHODS:We analyzed clinical and genetic sequence data from patients enrolled between 2016 and 2021 in the US multisite DCM Precision Medicine Study, which was a geographically diverse, multiracial, multiethnic cohort. Clinical evaluation included standardized patient interview and medical record query forms. DCM severity was classified into 3 groups: patients with advanced disease with LVAD/HT; patients with an implantable cardioverter defibrillator (ICD) only; or patients with no ICD or LVAD/HT. Rare variants in 36 DCM genes were classified as pathogenic or likely pathogenic or variants of uncertain significance. Confounding factors we considered included demographic characteristics, lifestyle factors, access to care, DCM duration, and comorbidities. Crude and adjusted associations between DCM severity and rare variant genetic findings were assessed using multinomial models with generalized logit link. RESULTS:Patients' mean (SD) age was 51.9 (13.6) years; 42% were of African ancestry, 56% were of European ancestry, and 44% were female. Of 1198 patients, 347 had LVAD/HT, 511 had an ICD, and 340 had no LVAD/HT or ICD. The percentage of patients with pathogenic or likely pathogenic variants was 26.2%, 15.9%, and 15.0% for those with LVAD/HT, ICD only, or neither, respectively. After controlling for sociodemographic characteristics and comorbidities, patients with DCM with LVAD/HT were more likely than those without LVAD/HT or ICD to have DCM-related pathogenic or likely pathogenic rare variants (odds ratio, 2.3 [95% CI, 1.5-3.6]). The association did not differ by ancestry. Rare variant genetic findings were similar between patients with DCM with an ICD and those without LVAD/HT or ICD. CONCLUSIONS:Advanced DCM was associated with higher odds of rare variants in DCM genes adjudicated as pathogenic or likely pathogenic, compared with individuals with less severe DCM. This finding may help assess the risk of outcomes in management of patients with DCM and their at-risk family members. REGISTRATION:URL: https://www. CLINICALTRIALS:gov; Unique identifier: NCT03037632.
PMID: 37641966
ISSN: 1524-4539
CID: 5598752

Risk of post-acute sequelae of SARS-CoV-2 infection associated with pre-coronavirus disease obstructive sleep apnea diagnoses: an electronic health record-based analysis from the RECOVER initiative

Mandel, Hannah L; Colleen, Gunnar; Abedian, Sajjad; Ammar, Nariman; Bailey, L Charles; Bennett, Tellen D; Brannock, M Daniel; Brosnahan, Shari B; Chen, Yu; Chute, Christopher G; Divers, Jasmin; Evans, Michael D; Haendel, Melissa; Hall, Margaret A; Hirabayashi, Kathryn; Hornig, Mady; Katz, Stuart D; Krieger, Ana C; Loomba, Johanna; Lorman, Vitaly; Mazzotti, Diego R; McMurry, Julie; Moffitt, Richard A; Pajor, Nathan M; Pfaff, Emily; Radwell, Jeff; Razzaghi, Hanieh; Redline, Susan; Seibert, Elle; Sekar, Anisha; Sharma, Suchetha; Thaweethai, Tanayott; Weiner, Mark G; Yoo, Yun Jae; Zhou, Andrea; Thorpe, Lorna E
STUDY OBJECTIVES/OBJECTIVE:Obstructive sleep apnea (OSA) has been associated with more severe acute coronavirus disease-2019 (COVID-19) outcomes. We assessed OSA as a potential risk factor for Post-Acute Sequelae of SARS-CoV-2 (PASC). METHODS:We assessed the impact of preexisting OSA on the risk for probable PASC in adults and children using electronic health record data from multiple research networks. Three research networks within the REsearching COVID to Enhance Recovery initiative (PCORnet Adult, PCORnet Pediatric, and the National COVID Cohort Collaborative [N3C]) employed a harmonized analytic approach to examine the risk of probable PASC in COVID-19-positive patients with and without a diagnosis of OSA prior to pandemic onset. Unadjusted odds ratios (ORs) were calculated as well as ORs adjusted for age group, sex, race/ethnicity, hospitalization status, obesity, and preexisting comorbidities. RESULTS:Across networks, the unadjusted OR for probable PASC associated with a preexisting OSA diagnosis in adults and children ranged from 1.41 to 3.93. Adjusted analyses found an attenuated association that remained significant among adults only. Multiple sensitivity analyses with expanded inclusion criteria and covariates yielded results consistent with the primary analysis. CONCLUSIONS:Adults with preexisting OSA were found to have significantly elevated odds of probable PASC. This finding was consistent across data sources, approaches for identifying COVID-19-positive patients, and definitions of PASC. Patients with OSA may be at elevated risk for PASC after SARS-CoV-2 infection and should be monitored for post-acute sequelae.
PMID: 37166330
ISSN: 1550-9109
CID: 5509392

Genetic Architecture of Dilated Cardiomyopathy in Individuals of African and European Ancestry

Jordan, Elizabeth; Kinnamon, Daniel D; Haas, Garrie J; Hofmeyer, Mark; Kransdorf, Evan; Ewald, Gregory A; Morris, Alanna A; Owens, Anjali; Lowes, Brian; Stoller, Douglas; Tang, W H Wilson; Garg, Sonia; Trachtenberg, Barry H; Shah, Palak; Pamboukian, Salpy V; Sweitzer, Nancy K; Wheeler, Matthew T; Wilcox, Jane E; Katz, Stuart; Pan, Stephen; Jimenez, Javier; Fishbein, Daniel P; Smart, Frank; Wang, Jessica; Gottlieb, Stephen S; Judge, Daniel P; Moore, Charles K; Mead, Jonathan O; Hurst, Natalie; Cao, Jinwen; Huggins, Gordon S; Cowan, Jason; Ni, Hanyu; Rehm, Heidi L; Jarvik, Gail P; Vatta, Matteo; Burke, Wylie; Hershberger, Ray E; ,
IMPORTANCE:Black patients with dilated cardiomyopathy (DCM) have increased familial risk and worse outcomes than White patients, but most DCM genetic data are from White patients. OBJECTIVE:To compare the rare variant genetic architecture of DCM by genomic ancestry within a diverse population of patients with DCM. DESIGN:Cross-sectional study enrolling patients with DCM who self-identified as non-Hispanic Black, Hispanic, or non-Hispanic White from June 7, 2016, to March 15, 2020, at 25 US advanced heart failure programs. Variants in 36 DCM genes were adjudicated as pathogenic, likely pathogenic, or of uncertain significance. EXPOSURE:Presence of DCM. MAIN OUTCOMES AND MEASURES:Variants in DCM genes classified as pathogenic/likely pathogenic/uncertain significance and clinically actionable (pathogenic/likely pathogenic). RESULTS:A total of 505, 667, and 26 patients with DCM of predominantly African, European, or Native American genomic ancestry, respectively, were included. Compared with patients of European ancestry, a lower percentage of patients of African ancestry had clinically actionable variants (8.2% [95% CI, 5.2%-11.1%] vs 25.5% [95% CI, 21.3%-29.6%]), reflecting the lower odds of a clinically actionable variant for those with any pathogenic variant/likely pathogenic variant/variant of uncertain significance (odds ratio, 0.25 [95% CI, 0.17-0.37]). On average, patients of African ancestry had fewer clinically actionable variants in TTN (difference, -0.09 [95% CI, -0.14 to -0.05]) and other genes with predicted loss of function as a disease-causing mechanism (difference, -0.06 [95% CI, -0.11 to -0.02]). However, the number of pathogenic variants/likely pathogenic variants/variants of uncertain significance was more comparable between ancestry groups (difference, -0.07 [95% CI, -0.22 to 0.09]) due to a larger number of non-TTN non-predicted loss of function variants of uncertain significance, mostly missense, in patients of African ancestry (difference, 0.15 [95% CI, 0.00-0.30]). Published clinical case-based evidence supporting pathogenicity was less available for variants found only in patients of African ancestry (P < .001). CONCLUSION AND RELEVANCE:Patients of African ancestry with DCM were less likely to have clinically actionable variants in DCM genes than those of European ancestry due to differences in genetic architecture and a lack of representation of African ancestry in clinical data sets.
PMID: 37526719
ISSN: 1538-3598
CID: 5594452

Development of a Definition of Postacute Sequelae of SARS-CoV-2 Infection

Thaweethai, Tanayott; Jolley, Sarah E; Karlson, Elizabeth W; Levitan, Emily B; Levy, Bruce; McComsey, Grace A; McCorkell, Lisa; Nadkarni, Girish N; Parthasarathy, Sairam; Singh, Upinder; Walker, Tiffany A; Selvaggi, Caitlin A; Shinnick, Daniel J; Schulte, Carolin C M; Atchley-Challenner, Rachel; Alba, George A; Alicic, Radica; Altman, Natasha; Anglin, Khamal; Argueta, Urania; Ashktorab, Hassan; Baslet, Gaston; Bassett, Ingrid V; Bateman, Lucinda; Bedi, Brahmchetna; Bhattacharyya, Shamik; Bind, Marie-Abele; Blomkalns, Andra L; Bonilla, Hector; Bush, Patricia A; Castro, Mario; Chan, James; Charney, Alexander W; Chen, Peter; Chibnik, Lori B; Chu, Helen Y; Clifton, Rebecca G; Costantine, Maged M; Cribbs, Sushma K; Davila Nieves, Sylvia I; Deeks, Steven G; Duven, Alexandria; Emery, Ivette F; Erdmann, Nathan; Erlandson, Kristine M; Ernst, Kacey C; Farah-Abraham, Rachael; Farner, Cheryl E; Feuerriegel, Elen M; Fleurimont, Judes; Fonseca, Vivian; Franko, Nicholas; Gainer, Vivian; Gander, Jennifer C; Gardner, Edward M; Geng, Linda N; Gibson, Kelly S; Go, Minjoung; Goldman, Jason D; Grebe, Halle; Greenway, Frank L; Habli, Mounira; Hafner, John; Han, Jenny E; Hanson, Keith A; Heath, James; Hernandez, Carla; Hess, Rachel; Hodder, Sally L; Hoffman, Matthew K; Hoover, Susan E; Huang, Beatrice; Hughes, Brenna L; Jagannathan, Prasanna; John, Janice; Jordan, Michael R; Katz, Stuart D; Kaufman, Elizabeth S; Kelly, John D; Kelly, Sara W; Kemp, Megan M; Kirwan, John P; Klein, Jonathan D; Knox, Kenneth S; Krishnan, Jerry A; Kumar, Andre; Laiyemo, Adeyinka O; Lambert, Allison A; Lanca, Margaret; Lee-Iannotti, Joyce K; Logarbo, Brian P; Longo, Michele T; Luciano, Carlos A; Lutrick, Karen; Maley, Jason H; Marathe, Jai G; Marconi, Vincent; Marshall, Gailen D; Martin, Christopher F; Matusov, Yuri; Mehari, Alem; Mendez-Figueroa, Hector; Mermelstein, Robin; Metz, Torri D; Morse, Richard; Mosier, Jarrod; Mouchati, Christian; Mullington, Janet; Murphy, Shawn N; Neuman, Robert B; Nikolich, Janko Z; Ofotokun, Ighovwerha; Ojemakinde, Elizabeth; Palatnik, Anna; Palomares, Kristy; Parimon, Tanyalak; Parry, Samuel; Patterson, Jan E; Patterson, Thomas F; Patzer, Rachel E; Peluso, Michael J; Pemu, Priscilla; Pettker, Christian M; Plunkett, Beth A; Pogreba-Brown, Kristen; Poppas, Athena; Quigley, John G; Reddy, Uma; Reece, Rebecca; Reeder, Harrison; Reeves, W B; Reiman, Eric M; Rischard, Franz; Rosand, Jonathan; Rouse, Dwight J; Ruff, Adam; Saade, George; Sandoval, Grecio J; Schlater, Shannon M; Shepherd, Fitzgerald; Sherif, Zaki A; Simhan, Hyagriv; Singer, Nora G; Skupski, Daniel W; Sowles, Amber; Sparks, Jeffrey A; Sukhera, Fatima I; Taylor, Barbara S; Teunis, Larissa; Thomas, Robert J; Thorp, John M; Thuluvath, Paul; Ticotsky, Amberly; Tita, Alan T; Tuttle, Katherine R; Urdaneta, Alfredo E; Valdivieso, Daisy; VanWagoner, Timothy M; Vasey, Andrew; Verduzco-Gutierrez, Monica; Wallace, Zachary S; Ward, Honorine D; Warren, David E; Weiner, Steven J; Welch, Shelley; Whiteheart, Sidney W; Wiley, Zanthia; Wisnivesky, Juan P; Yee, Lynn M; Zisis, Sokratis; Horwitz, Leora I; Foulkes, Andrea S
IMPORTANCE:SARS-CoV-2 infection is associated with persistent, relapsing, or new symptoms or other health effects occurring after acute infection, termed postacute sequelae of SARS-CoV-2 infection (PASC), also known as long COVID. Characterizing PASC requires analysis of prospectively and uniformly collected data from diverse uninfected and infected individuals. OBJECTIVE:To develop a definition of PASC using self-reported symptoms and describe PASC frequencies across cohorts, vaccination status, and number of infections. DESIGN, SETTING, AND PARTICIPANTS:Prospective observational cohort study of adults with and without SARS-CoV-2 infection at 85 enrolling sites (hospitals, health centers, community organizations) located in 33 states plus Washington, DC, and Puerto Rico. Participants who were enrolled in the RECOVER adult cohort before April 10, 2023, completed a symptom survey 6 months or more after acute symptom onset or test date. Selection included population-based, volunteer, and convenience sampling. EXPOSURE:SARS-CoV-2 infection. MAIN OUTCOMES AND MEASURES:PASC and 44 participant-reported symptoms (with severity thresholds). RESULTS:A total of 9764 participants (89% SARS-CoV-2 infected; 71% female; 16% Hispanic/Latino; 15% non-Hispanic Black; median age, 47 years [IQR, 35-60]) met selection criteria. Adjusted odds ratios were 1.5 or greater (infected vs uninfected participants) for 37 symptoms. Symptoms contributing to PASC score included postexertional malaise, fatigue, brain fog, dizziness, gastrointestinal symptoms, palpitations, changes in sexual desire or capacity, loss of or change in smell or taste, thirst, chronic cough, chest pain, and abnormal movements. Among 2231 participants first infected on or after December 1, 2021, and enrolled within 30 days of infection, 224 (10% [95% CI, 8.8%-11%]) were PASC positive at 6 months. CONCLUSIONS AND RELEVANCE:A definition of PASC was developed based on symptoms in a prospective cohort study. As a first step to providing a framework for other investigations, iterative refinement that further incorporates other clinical features is needed to support actionable definitions of PASC.
PMID: 37278994
ISSN: 1538-3598
CID: 5536662

Screening for Dilated Cardiomyopathy in At-Risk First-Degree Relatives

Ni, Hanyu; Jordan, Elizabeth; Kinnamon, Daniel D; Cao, Jinwen; Haas, Garrie J; Hofmeyer, Mark; Kransdorf, Evan; Ewald, Gregory A; Morris, Alanna A; Owens, Anjali; Lowes, Brian; Stoller, Douglas; Tang, W H Wilson; Garg, Sonia; Trachtenberg, Barry H; Shah, Palak; Pamboukian, Salpy V; Sweitzer, Nancy K; Wheeler, Matthew T; Wilcox, Jane E; Katz, Stuart; Pan, Stephen; Jimenez, Javier; Fishbein, Daniel P; Smart, Frank; Wang, Jessica; Gottlieb, Stephen S; Judge, Daniel P; Moore, Charles K; Huggins, Gordon S; Hershberger, Ray E
BACKGROUND:Cardiovascular screening is recommended for first-degree relatives (FDRs) of patients with dilated cardiomyopathy (DCM), but the yield of FDR screening is uncertain for DCM patients without known familial DCM, for non-White FDRs, or for DCM partial phenotypes of left ventricular enlargement (LVE) or left ventricular systolic dysfunction (LVSD). OBJECTIVES:This study examined the yield of clinical screening among reportedly unaffected FDRs of DCM patients. METHODS:Adult FDRs of DCM patients at 25 sites completed screening echocardiograms and ECGs. Mixed models accounting for site heterogeneity and intrafamilial correlation were used to compare screen-based percentages of DCM, LVSD, or LVE by FDR demographics, cardiovascular risk factors, and proband genetics results. RESULTS:A total of 1,365 FDRs were included, with a mean age of 44.8 ± 16.9 years, 27.5% non-Hispanic Black, 9.8% Hispanic, and 61.7% women. Among screened FDRs, 14.1% had new diagnoses of DCM (2.1%), LVSD (3.6%), or LVE (8.4%). The percentage of FDRs with new diagnoses was higher for those aged 45 to 64 years than 18 to 44 years. The age-adjusted percentage of any finding was higher among FDRs with hypertension and obesity but did not differ statistically by race and ethnicity (16.2% for Hispanic, 15.2% for non-Hispanic Black, and 13.1% for non-Hispanic White) or sex (14.6% for women and 12.8% for men). FDRs whose probands carried clinically reportable variants were more likely to be identified with DCM. CONCLUSIONS:Cardiovascular screening identified new DCM-related findings among 1 in 7 reportedly unaffected FDRs regardless of race and ethnicity, underscoring the value of clinical screening in all FDRs.
PMID: 37225358
ISSN: 1558-3597
CID: 5503782