Research Spotlight

Muller, D.W.M., Sorajja, P., Duncan, A., Bethea, B., Dahle, G., Grayburn, P., Babaliaros, V., Guerrero, M., Thourani, V.H., Bedogni, F., Denti, P., Dumonteil, N., Modine, T., Jansz, P., Chuang, M.L., Blanke, P., Leipsic, J. and Badhwar, V. (2021). “2-Year Outcomes of Transcatheter Mitral Valve Replacement in Patients With Severe Symptomatic Mitral Regurgitation.” J Am Coll Cardiol 78(19): 1847-1859.

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BACKGROUND: Transcatheter mitral valve replacement (TMVR) is feasible for selected patients with severe mitral regurgitation (MR) who are poor candidates for valve surgery. Intermediate-term to long-term TMVR outcomes have not been reported. OBJECTIVES: This study sought to evaluate the safety and effectiveness through 2-year follow-up of TMVR in high-surgical-risk patients with severe MR. METHODS: The first 100 patients enrolled in the Expanded Clinical Study of the Tendyne Mitral Valve System, an open-label, nonrandomized, prospective study of transapical TMVR, were followed for 2 years. RESULTS: The patients (aged 74.7 ± 8.0 years, 69.0% male) had symptomatic (66.0% New York Heart Association [NYHA] functional class III or IV) grade 3+ or 4+ MR that was secondary or mixed in 89 (89.0%). Prostheses were successfully implanted in 97 (97.0%) patients. At 2 years, all-cause mortality was 39.0%; 17 (43.6%) of 39 deaths occurred during the first 90 days. Heart failure hospitalization (HFH) fell from 1.30 events per year preprocedure to 0.51 per year in the 2 years post-TMVR (P < 0.0001). At 2 years, 93.2% of surviving patients had no MR. No patient had >1+ MR. The improvement in symptoms at 1 year (88.5% NYHA functional class I or II) was sustained to 2 years (81.6% NYHA functional class I or II). Among survivors, the left ventricular ejection fraction was 45.6 ± 9.4% at baseline and 39.8 ± 9.5% at 2 years (P = 0.0012). Estimated right ventricular systolic pressure decreased from 47.6 ± 8.6 mm Hg to 32.5 ± 10.4 mm Hg (P < 0.005). CONCLUSIONS: In this study, the impact of TMVR on severity of MR, reduction in HFH rate, and improvement in symptoms was sustained through 2 years. All-cause mortality and the need for HFH was highest in the first 3 months postprocedure. (Expanded Clinical Study of the Tendyne Mitral Valve System; NCT02321514).

Garrett, J., Vanston, A., Ogola, G., da Graca, B., Cassity, C., Kouznetsova, M.A., Hall, L.R. and Qiu, T. (2021). “Predicting opioid-induced oversedation in hospitalised patients: a multicentre observational study.” BMJ Open 11(11): e051663.

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OBJECTIVES: Opioid-induced respiratory depression (OIRD) and oversedation are rare but potentially devastating adverse events in hospitalised patients. We investigated which features predict an individual patient’s risk of OIRD or oversedation; and developed a risk stratification tool that can be used to aid point-of-care clinical decision-making. DESIGN: Retrospective observational study. SETTING: Twelve acute care hospitals in a large not-for-profit integrated delivery system. PARTICIPANTS: All inpatients ≥18 years admitted between 1 July 2016 and 30 June 2018 who received an opioid during their stay (163 190 unique hospitalisations). MAIN OUTCOME MEASURES: The primary outcome was occurrence of sedation or respiratory depression severe enough that emergent reversal with naloxone was required, as determined from medical record review; if naloxone reversal was unsuccessful or if there was no evidence of hypoxic encephalopathy or death due to oversedation, it was not considered an oversedation event. RESULTS: Age, sex, body mass index, chronic obstructive pulmonary disease, concurrent sedating medication, renal insufficiency, liver insufficiency, opioid naïvety, sleep apnoea and surgery were significantly associated with risk of oversedation. The strongest predictor was concurrent administration of another sedating medication (adjusted HR, 95% CI=3.88, 2.48 to 6.06); the most common such medications were benzodiazepines (29%), antidepressants (22%) and gamma-aminobutyric acid analogue (14.7%). The c-statistic for the final model was 0.755. The 24-point Oversedation Risk Criteria (ORC) score developed from the model stratifies patients as high (>20%, ≥21 points), moderate (11%-20%, 10-20 points) and low risk (≤10%, <10 points). CONCLUSIONS: The ORC risk score identifies patients at high risk for OIRD or oversedation from routinely collected data, enabling targeted monitoring for early detection and intervention. It can also be applied to preventive strategies-for example, clinical decision support offered when concurrent prescriptions for opioids and other sedating medications are entered that shows how the chosen combination impacts the patient's risk.

Tenforde, M.W., Self, W.H., Adams, K., Gaglani, M., Ginde, A.A., McNeal, T., Ghamande, S., Douin, D.J., Talbot, H.K., Casey, J.D., Mohr, N.M., Zepeski, A., Shapiro, N.I., Gibbs, K.W., Files, D.C., Hager, D.N., Shehu, A., Prekker, M.E., Erickson, H.L., Exline, M.C., Gong, M.N., Mohamed, A., Henning, D.J., Steingrub, J.S., Peltan, I.D., Brown, S.M., Martin, E.T., Monto, A.S., Khan, A., Hough, C.L., Busse, L.W., Ten Lohuis, C.C., Duggal, A., Wilson, J.G., Gordon, A.J., Qadir, N., Chang, S.Y., Mallow, C., Rivas, C., Babcock, H.M., Kwon, J.H., Halasa, N., Chappell, J.D., Lauring, A.S., Grijalva, C.G., Rice, T.W., Jones, I.D., Stubblefield, W.B., Baughman, A., Womack, K.N., Rhoads, J.P., Lindsell, C.J., Hart, K.W., Zhu, Y., Olson, S.M., Kobayashi, M., Verani, J.R. and Patel, M.M. (2021). “Association Between mRNA Vaccination and COVID-19 Hospitalization and Disease Severity.” Jama 326(20): 2043-2054.

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IMPORTANCE: A comprehensive understanding of the benefits of COVID-19 vaccination requires consideration of disease attenuation, determined as whether people who develop COVID-19 despite vaccination have lower disease severity than unvaccinated people. OBJECTIVE: To evaluate the association between vaccination with mRNA COVID-19 vaccines-mRNA-1273 (Moderna) and BNT162b2 (Pfizer-BioNTech)-and COVID-19 hospitalization, and, among patients hospitalized with COVID-19, the association with progression to critical disease. DESIGN, SETTING, AND PARTICIPANTS: A US 21-site case-control analysis of 4513 adults hospitalized between March 11 and August 15, 2021, with 28-day outcome data on death and mechanical ventilation available for patients enrolled through July 14, 2021. Date of final follow-up was August 8, 2021. EXPOSURES: COVID-19 vaccination. MAIN OUTCOMES AND MEASURES: Associations were evaluated between prior vaccination and (1) hospitalization for COVID-19, in which case patients were those hospitalized for COVID-19 and control patients were those hospitalized for an alternative diagnosis; and (2) disease progression among patients hospitalized for COVID-19, in which cases and controls were COVID-19 patients with and without progression to death or mechanical ventilation, respectively. Associations were measured with multivariable logistic regression. RESULTS: Among 4513 patients (median age, 59 years [IQR, 45-69]; 2202 [48.8%] women; 23.0% non-Hispanic Black individuals, 15.9% Hispanic individuals, and 20.1% with an immunocompromising condition), 1983 were case patients with COVID-19 and 2530 were controls without COVID-19. Unvaccinated patients accounted for 84.2% (1669/1983) of COVID-19 hospitalizations. Hospitalization for COVID-19 was significantly associated with decreased likelihood of vaccination (cases, 15.8%; controls, 54.8%; adjusted OR, 0.15; 95% CI, 0.13-0.18), including for sequenced SARS-CoV-2 Alpha (8.7% vs 51.7%; aOR, 0.10; 95% CI, 0.06-0.16) and Delta variants (21.9% vs 61.8%; aOR, 0.14; 95% CI, 0.10-0.21). This association was stronger for immunocompetent patients (11.2% vs 53.5%; aOR, 0.10; 95% CI, 0.09-0.13) than immunocompromised patients (40.1% vs 58.8%; aOR, 0.49; 95% CI, 0.35-0.69) (P < .001) and weaker at more than 120 days since vaccination with BNT162b2 (5.8% vs 11.5%; aOR, 0.36; 95% CI, 0.27-0.49) than with mRNA-1273 (1.9% vs 8.3%; aOR, 0.15; 95% CI, 0.09-0.23) (P < .001). Among 1197 patients hospitalized with COVID-19, death or invasive mechanical ventilation by day 28 was associated with decreased likelihood of vaccination (12.0% vs 24.7%; aOR, 0.33; 95% CI, 0.19-0.58). CONCLUSIONS AND RELEVANCE: Vaccination with an mRNA COVID-19 vaccine was significantly less likely among patients with COVID-19 hospitalization and disease progression to death or mechanical ventilation. These findings are consistent with risk reduction among vaccine breakthrough infections compared with absence of vaccination.

Edwards, L.J., Fowlkes, A.L., Wesley, M.G., Kuntz, J.L., Odean, M.J., Caban-Martinez, A.J., Dunnigan, K., Phillips, A.L., Grant, L., Herring, M.K., Groom, H.C., Respet, K., Beitel, S., Zunie, T., Hegmann, K.T., Kumar, A., Joseph, G., Poe, B., Louzado-Feliciano, P., Smith, M.E., Thiese, M.S., Schaefer-Solle, N., Yoo, Y.M., Silvera, C.A., Mayo Lamberte, J., Mak, J., McDonald, L.C., Stuckey, M.J., Kutty, P., Arvay, M.L., Yoon, S.K., Tyner, H.L., Burgess, J.L., Hunt, D.R., Meece, J., Gaglani, M., Naleway, A.L. and Thompson, M.G. (2021). “Research on the Epidemiology of SARS-CoV-2 in Essential Response Personnel (RECOVER): Protocol for a Multisite Longitudinal Cohort Study.” JMIR Res Protoc 10(12): e31574.

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BACKGROUND: Workers critical to emergency response and continuity of essential services during the COVID-19 pandemic are at a disproportionally high risk of SARS-CoV-2 infection. Prospective cohort studies are needed for enhancing the understanding of the incidence of symptomatic and asymptomatic SARS-CoV-2 infections, identifying risk factors, assessing clinical outcomes, and determining the effectiveness of vaccination. OBJECTIVE: The Research on the Epidemiology of SARS-CoV-2 in Essential Response Personnel (RECOVER) prospective cohort study was designed to estimate the incidence of symptomatic and asymptomatic SARS-CoV-2 infections, examine the risk factors for infection and clinical spectrum of illness, and assess the effectiveness of vaccination among essential workers. METHODS: The RECOVER multisite network was initiated in August 2020 and aims to enroll 3000 health care personnel (HCP), first responders, and other essential and frontline workers (EFWs) at 6 US locations. Data on participant demographics, medical history, and vaccination history are collected at baseline and throughout the study. Active surveillance for the symptoms of COVID-19-like illness (CLI), access of medical care, and symptom duration is performed by text messages, emails, and direct participant or medical record reports. Participants self-collect a mid-turbinate nasal swab weekly, regardless of symptoms, and 2 additional respiratory specimens at the onset of CLI. Blood is collected upon enrollment, every 3 months, approximately 28 days after a reverse transcription polymerase chain reaction (RT-PCR)-confirmed SARS-CoV-2 infection, and 14 to 28 days after a dose of any COVID-19 vaccine. From February 2021, household members of RT-PCR-confirmed participants are self-collecting mid-turbinate nasal swabs daily for 10 days. RESULTS: The study observation period began in August 2020 and is expected to continue through spring 2022. There are 2623 actively enrolled RECOVER participants, including 280 participants who have been found to be positive for SARS-CoV-2 by RT-PCR. Enrollment is ongoing at 3 of the 6 study sites. CONCLUSIONS: Data collected through the cohort are expected to provide important public health information for essential workers at high risk for occupational exposure to SARS-CoV-2 and allow early evaluation of COVID-19 vaccine effectiveness. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/31574.

Ibrahim, S.F., Kasprzak, J.M., Hall, M.A., Fitzgerald, A.L., Siegel, J.J., Kurley, S.J., Covington, K.R., Goldberg, M.S., Farberg, A.S., Trotter, S.C., Reed, K., Brodland, D.G., Koyfman, S.A., Somani, A.K., Arron, S.T. and Wysong, A. (2021). “Enhanced metastatic risk assessment in cutaneous squamous cell carcinoma with the 40-gene expression profile test.” Future Oncol Nov 25. [Epub ahead of print].

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Aim: To clinically validate the 40-gene expression profile (40-GEP) test for cutaneous squamous cell carcinoma patients and evaluate coupling the test with individual clinicopathologic risk factor-based assessment methods. Patients & methods: In a 33-site study, primary tumors with known patient outcomes were assessed under clinical testing conditions (n = 420). The 40-GEP results were integrated with clinicopathologic risk factors. Kaplan-Meier and Cox regression analyses were performed for metastasis. Results: The 40-GEP test demonstrated significant prognostic value. Risk classification was improved via integration of 40-GEP results with clinicopathologic risk factor-based assessment, with metastasis rates near the general cutaneous squamous cell carcinoma population for Class 1 and ≥50% for Class 2B. Conclusion: Combining molecular profiling with clinicopathologic risk factor assessment enhances stratification of cutaneous squamous cell carcinoma patients and may inform decision-making for risk-appropriate management strategies.