Effect of Routine Invasive vs Conservative Strategy in Older Adults With Frailty and Non-ST-Segment Elevation Acute Myocardial Infarction: A Randomized Clinical Trial.

Importance: To our knowledge, no randomized clinical trial has compared the invasive and conservative strategies in frail, older patients with non-ST-segment elevation acute myocardial infarction (NSTEMI). Objective: To compare outcomes of invasive and conservative strategies in frail, older patients with NSTEMI at 1 year. Design, Setting, and Participants: This multicenter randomized clinical trial was conducted at 13 Spanish hospitals between July 7, 2017, and January 9, 2021, and included 167 older adult (≥70 years) patients with frailty (Clinical Frailty Scale score ≥4) and NSTEMI. Data analysis was performed from April 2022 to June 2022. Interventions: Patients were randomized to routine invasive (coronary angiography and revascularization if feasible; n = 84) or conservative (medical treatment with coronary angiography for recurrent ischemia; n = 83) strategy. Main Outcomes and Measures: The primary end point was the number of days alive and out of the hospital (DAOH) from discharge to 1 year. The coprimary end point was the composite of cardiac death, reinfarction, or postdischarge revascularization. Results: The study was prematurely stopped due to the COVID-19 pandemic when 95% of the calculated sample size had been enrolled. Among the 167 patients included, the mean (SD) age was 86 (5) years, and mean (SD) Clinical Frailty Scale score was 5 (1). While not statistically different, DAOH were about 1 month (28 days; 95% CI, -7 to 62) greater for patients managed conservatively (312 days; 95% CI, 289 to 335) vs patients managed invasively (284 days; 95% CI, 255 to 311; P = .12). A sensitivity analysis stratified by sex did not show differences. In addition, we found no differences in all-cause mortality (hazard ratio, 1.45; 95% CI, 0.74-2.85; P = .28). There was a 28-day shorter survival in the invasive vs conservatively managed group (95% CI, -63 to 7 days; restricted mean survival time analysis). Noncardiac reasons accounted for 56% of the readmissions. There were no differences in the number of readmissions or days spent in the hospital after discharge between groups. Neither were there differences in the coprimary end point of ischemic cardiac events (subdistribution hazard ratio, 0.92; 95% CI, 0.54-1.57; P = .78). Conclusions and Relevance: In this randomized clinical trial of NSTEMI in frail older patients, there was no benefit to a routine invasive strategy in DAOH during the first year. Based on these findings, a policy of medical management and watchful observation is recommended for older patients with frailty and NSTEMI. Trial Registration: ClinicalTrials.gov Identifier: NCT03208153.

Effect of a home-based inspiratory muscle training programme on functional capacity in postdischarged patients with long COVID: the InsCOVID trial.

BACKGROUND: Fatigue and exercise intolerance are the most common symptoms in patients with long COVID. AIMS: This study aimed to evaluate whether a home-based inspiratory muscle training (IMT) programme improves maximal functional capacity in patients' long COVID after a previous admission due to SARS-CoV-2 pneumonia. METHODS: This study was a single-centre, blinded assessor, randomised controlled trial. Twenty-six patients with long COVID and a previous admission due to SARS-CoV-2 pneumonia were randomly assigned to receive either a 12-week IMT or usual care alone (NCT05279430). The physiotherapist and participants were not blinded. Patients allocated to the IMT arm were instructed to train at home twice daily using a threshold inspiratory muscle trainer and to maintain diaphragmatic breathing during the training session. The usual care arm received no intervention.The primary endpoint was the change in peak oxygen consumption (peakVO2). Secondary endpoints were changes in quality of life (QoL), ventilatory efficiency and chronotropic response during exercise (evaluated by chronotropic index-CIx- formula). We used linear mixed regression analysis for evaluating changes in primary and secondary endpoints. RESULTS: The mean age of the sample and time to first visit after discharge were 50.4±12.2 years and 362±105 days, respectively. A total of 11 (42.3%) were female. At baseline, the mean of peakVO2, ventilatory efficiency and CIx were 18.9±5 mL/kg/min, 29.4±5.2 and 0.64±0.19, respectively. The IMT arm improved their peakVO2 significantly compared with usual care (+Δ 4.46 mL/kg/min, 95% CI 3.10 to 5.81; p<0.001). Similar positive findings were found when evaluating changes for CIx and some QoL dimensions. We did not find significant changes in ventilatory efficiency. CONCLUSION: In long COVID patients with a previous admission due to SARS-CoV-2 pneumonia, IMT was associated with marked improvement in exercise capacity and QoL. TRIAL REGISTRATION NUMBER: NCT05279430.

Early carbohydrate antigen 125 as a mortality predictor in hospitalized patients with coronavirus disease 2019.

Background: Carbohydrate antigen 125 (CA125) is an indicator of inflammation, immune response, and impaired cardiac function. The aim was to investigate whether CA125 behaves as a biomarker of severity and poor clinical outcomes in hospitalized patients with coronavirus disease 2019 (COVID-19). Methods: Serum CA125 [Elecsys CA125 II assay-(Roche Diagnostics GmbH)] was measured in stored biobank samples from COVID-19 hospitalized patients between 01 March 2020 and 17 October 2021. Multiple logistic regression models were built to explore the association between CA125 and clinical outcomes [in-hospital all-cause mortality, need for invasive mechanical ventilation (IMV), or non-invasive respiratory support (non-IRS)], estimating odds ratios (ORs; 95% CI). The gradient of risk of CA125 was evaluated by fractional polynomials. Results: A total of 691 patients were included, median age of 63 years (50-76), men (57.2%), with high comorbidity. At admission, 85.8% had pneumonia. Median CA125 was 10.33 U/ml (7.48-15.50). The in-hospital mortality rate was 7.2%. After adjusting for confounding factors, CA125 ≥ 15.5 U/ml (75th percentile) showed an increased risk of death [OR 2.85(1.21-6.71)], as age ≥ 65 years, diabetes, and immunosuppression. Furthermore, CA125 as a continuous variable was positive and significantly associated with the risk of death after multivariate adjustment. The mean hospital stay of the patients with CA125 ≥ 15.5 U/ml was longer than the rest of the study population. Conclusion: CA125 in the first 72 h of hospital admission seems a useful biomarker of mortality in hospitalized patients with moderate-severe COVID-19. If our findings are confirmed, the wide availability of this biomarker would make easy its widespread implementation in clinical practice.

Effect of a home-based inspiratory muscular training programme on functional capacity in patients with chronic COVID-19 after a hospital discharge: protocol for a randomised control trial (InsCOVID trial).

INTRODUCTION: Exercise intolerance and fatigue are the most common symptoms in patients with chronic COVID-19 after hospital discharge. Supervised exercise training programmes improve symptoms, but scarce research has been done on home-based exercise programmes on the maximal functional capacity for discharged symptomatic COVID-19 patients. This study evaluates whether a home-based inspiratory muscle training (IMT) programme improves maximal functional capacity in chronic COVID-19 after hospital admission. METHODS AND ANALYSIS: This single-centre, assessor-blinded randomised controlled trial, powered for superiority, seeks to evaluate maximal functional capacity as the primary endpoint. A total of 26 eligible patients with a previous admission for acute respiratory syndrome coronavirus 2 pneumonia (>3 months after hospital discharge) will be randomised (1:1) to receive a 12-week programme of IMT versus usual care alone. A blinded assessor will measure outcomes at baseline and after the intervention (12 weeks). An analysis of variance will be used to compare continuous outcomes among the two-intervention groups. As of 21 March 2022, eight patients have been enrolled. ETHICS AND DISSEMINATION: The research ethics committee (Comité Ético de Investigación con Medicamentos de l'Hospital Clínic Universitari de València) approved the protocol following the principles of the Declaration of Helsinki and national regulations (Approval Number: 021/226). Findings will be published in peer-reviewed journals and conference publications. TRIAL REGISTRATION NUMBER: NCT05279430.

Mortality associated with cardiovascular disease in patients with COVID-19

Introduction and objectives: Cardiovascular disease (CVD) has been outlined as a possible risk factor for poorer outcomes in patients with COVID-19 infection. Methods: A meta-analysis was performed with currently available studies that report the prevalence of CVD in survivors vs non-survivors in patients with COVID-19 infection using reports available at 16 July 2020. Analyses were performed by a random effects model and sensitivity analyses were performed for the identification of potential sources of heterogeneity or assess the small-study effects. Results: A total of 307 596 patients from 16 reports were included and 46 321 (15.1%) had CVD. Globally, mortality rate was 8.2% (20 534 patients) and mortality rates were higher in hospital registries (48.7%) compared to national reports (23.1%). A total of 11 213 (24.2%) patients with CVD died and mortality rates were also higher in hospital registries (48.7%) compared to national reports (23.1%). CVD was associated to 4-fold higher risk of mortality (OR, 4.33;95%CI, 3.16-5.94). Data from 28 048 patients with diabetes was available. Diabetes was associated to higher mortality risk (OR, 2.41;95%CI, 1.79-3.26;P < .001). From 40 173 subjects with hypertension it could also be proven a risk factor for higher mortality (OR, 2.60;95%CI, 2.10-3.21;P < .001). Conclusions: patients with CVD and COVID-19 infection have 4-fold higher risk of death. Diabetes or hypertension are also associated with higher mortality risk. Resumen Introducción y objetivos: Las enfermedades cardiovasculares (ECV) se han identificado como un factor de riesgo de mal pronóstico en pacientes con infección por COVID-19. Métodos: Se realizó un metanálisis de estudios actualmente disponibles con la prevalencia de ECV en supervivientes frente a no supervivientes en pacientes con infección por COVID-19 hasta el 16 de julio de 2020. Los análisis se realizaron mediante un modelo de efectos aleatorios y sensibilidad. Se realizaron análisis para identificar posibles fuentes de heterogeneidad o evaluar los efectos de los estudios pequeños. Resultados: Se incluyó a 307.596 pacientes de 16 estudios, de los que 46.321 (15,1%) tenían ECV. La tasa de mortalidad fue del 8,2% (20.534 pacientes) y fue superior en los registros hospitalarios (48,7%) en comparación con los informes nacionales (23,1%). Un total de 11.213 (24,2%) pacientes con ECV fallecieron y las tasas de mortalidad también fueron más altas en los registros hospitalarios (48,7%) en comparación con los informes nacionales (23,1%). La ECV se asoció con un riesgo de mortalidad 4 veces mayor (OR, 4,33;IC95%, 3,16-5,94). Se disponía de datos de 28.048 pacientes con diabetes que también se asoció a un mayor riesgo de mortalidad (OR, 2,41;IC95%, 1,79-3,26;p < 0,001). De 40.173 pacientes con hipertensión, también se concluyó que era un factor de riesgo de mayor mortalidad (OR, 2,60, IC95%, 2,10-3,21;p < 0,001). Conclusiones: Los pacientes con ECV e infección por COVID-19 tienen un riesgo 4 veces mayor de muerte. La diabetes y la hipertensión arterial también son factores de mayor riesgo en los pacientes con COVID-19.

The Effect of Age on Mortality in Patients With COVID-19: A Meta-Analysis With 611,583 Subjects.

OBJECTIVES: Initial data on COVID-19 infection has pointed out a special vulnerability of older adults. DESIGN: We performed a meta-analysis with available national reports on May 7, 2020 from China, Italy, Spain, United Kingdom, and New York State. Analyses were performed by a random effects model, and sensitivity analyses were performed for the identification of potential sources of heterogeneity. SETTING AND PARTICIPANTS: COVID-19-positive patients reported in literature and national reports. MEASURES: All-cause mortality by age. RESULTS: A total of 611,1583 subjects were analyzed and 141,745 (23.2%) were aged ≥80 years. The percentage of octogenarians was different in the 5 registries, the lowest being in China (3.2%) and the highest in the United Kingdom and New York State. The overall mortality rate was 12.10% and it varied widely between countries, the lowest being in China (3.1%) and the highest in the United Kingdom (20.8%) and New York State (20.99%). Mortality was <1.1% in patients aged <50 years and it increased exponentially after that age in the 5 national registries. As expected, the highest mortality rate was observed in patients aged ≥80 years. All age groups had significantly higher mortality compared with the immediately younger age group. The largest increase in mortality risk was observed in patients aged 60 to 69 years compared with those aged 50 to 59 years (odds ratio 3.13, 95% confidence interval 2.61-3.76). CONCLUSIONS AND IMPLICATIONS: This meta-analysis with more than half million of COVID-19 patients from different countries highlights the determinant effect of age on mortality with the relevant thresholds on age >50 years and, especially, >60 years. Older adult patients should be prioritized in the implementation of preventive measures.