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First-Phase Ejection Fraction, a Measure of Preclinical Heart Failure, Is Strongly Associated With Increased Mortality in Patients With COVID-19.

ABSTRACT: Presence of heart failure is associated with a poor prognosis in patients with coronavirus disease 2019 (COVID-19). The aim of the present study was to examine whether first-phase ejection fraction (EF1), the ejection fraction measured in early systole up to the time of peak aortic velocity, a sensitive measure of preclinical heart failure, is associated with survival in patients hospitalized with COVID-19. A retrospective outcome study was performed in patients hospitalized with COVID-19 who underwent echocardiography (n=380) at the West Branch of the Union Hospital, Wuhan, China and in patients admitted to King's Health Partners in South London, United Kingdom. Association of EF1 with survival was performed using Cox proportional hazards regression. EF1 was compared in patients with COVID-19 and in historical controls with similar comorbidities (n=266) who had undergone echocardiography before the COVID-19 pandemic. In patients with COVID-19, EF1 was a strong predictor of survival in each patient group (Wuhan and London). In the combined group, EF1 was a stronger predictor of survival than other clinical, laboratory, and echocardiographic characteristics including age, comorbidities, and biochemical markers. A cutoff value of 25% for EF1 gave a hazard ratio of 5.23 ([95% CI, 2.85-9.60]; P<0.001) unadjusted and 4.83 ([95% CI, 2.35-9.95], P<0.001) when adjusted for demographics, comorbidities, hs-cTnI (high-sensitive cardiac troponin), and CRP (C-reactive protein). EF1 was similar in patients with and without COVID-19 (23.2±7.3 versus 22.0±7.6%, P=0.092, adjusted for prevalence of risk factors and comorbidities). Impaired EF1 is strongly associated with mortality in COVID-19 and probably reflects preexisting, preclinical heart failure.

SUBMITTER: Gu H

PROVIDER: S-EPMC8115431 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature

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First-Phase Ejection Fraction, a Measure of Preclinical Heart Failure, Is Strongly Associated With Increased Mortality in Patients With COVID-19.

Gu Haotian H Cirillo Chiara C Cirillo Chiara C Nabeebaccus Adam A AA Sun Zhenxing Z Fang Lingyun L Xie Yuji Y Demir Ozan O Desai Nishita N He Lin L Lü Qing Q Nakou Eleni E O'Gallagher Kevin K Tountas Christos C Marvaki Apostolia A Monaghan Mark M Perera Divaka D Pericao Ana A Ryan Matthew M Sinclair Hannah H Stylianidis Vasileios V Victor Kelly K Wang Bin B Wang Jing J Wang Rui R Wu Chun C Yang Yali Y Yuan Hongliang H Zhang Danqing D Zhang Yongxing Y Faconti Luca L Papachristidis Alexandros A Zhang Li L Carr-White Gerald G Shah Ajay M AM Xie Mingxing M Chowienczyk Phil P

Hypertension (Dallas, Tex. : 1979) 20210510 6

Presence of heart failure is associated with a poor prognosis in patients with coronavirus disease 2019 (COVID-19). The aim of the present study was to examine whether first-phase ejection fraction (EF1), the ejection fraction measured in early systole up to the time of peak aortic velocity, a sensitive measure of preclinical heart failure, is associated with survival in patients hospitalized with COVID-19. A retrospective outcome study was performed in patients hospitalized with COVID-19 who un ...[more]

PMID: 33966447

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Project description:AimsThe proportion of patients hospitalized for heart failure (HF) with preserved left ventricular ejection fraction (LVEF) is rising, but no approved treatment exists, in part owing to incomplete characterization of this particular HF phenotype. In order to better define the characteristics of HF phenotypes in Finland, a large cohort with 12 years' follow-up time was analysed.Methods and resultsPatients diagnosed between 2005 and 2017 at the Hospital District of Southwest Finland were stratified according to LVEF measure and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels. For this retrospective registry study, previously diagnosed HF patients were defined as follows: patients with reduced ejection fraction (HFrEF; LVEF ≤ 40%; n = 4042), mid-range ejection fraction (HFmrEF; LVEF > 40-50% and NT-proBNP ≥ 125 pg/mL; n = 1468), and preserved ejection fraction (HFpEF; LVEF > 50% and NT-proBNP ≥ 125 pg/mL; n = 3122) and followed up for 15 022, 4962, and 10 097 patient-years, respectively. Cardiovascular (CV) hospitalization and mortality, influence of pre-selected covariates on hospitalization and mortality, and the proportion of HFpEF and HFmrEF patients with a drop in LVEF to HFrEF phenotype were analysed. All data were extracted from the electronic patient register. HFrEF patients were rehospitalized slightly earlier than HFpEF/HFmrEF patients, but the second, third, and fourth rehospitalization rates did not differ between the subgroups. Female gender and better kidney function were associated with reduced rehospitalizations in HFmrEF and HFrEF, with a non-significant trend in HFpEF. Each additional hospitalization was associated with a two-fold increased risk of death and 2.2- to 2.3-fold increased risk of CV death. All-cause mortality was higher in patients with HFpEF. Although CV mortality was less frequent in HFpEF patients, it was associated with increased NT-proBNP concentrations at index in all patient groups. During the 10 years following the index date, 26% of HFmrEF patients and 10% of HFpEF patients progressed to an HFrEF phenotype.ConclusionsThese findings suggest that disease progression, in terms of increased frequency of hospitalizations, and the relationship between increased number of hospitalizations and mortality are similar by LVEF phenotypes. These data highlight the importance of effective treatments that can reduce hospitalizations and suggest a role for monitoring NT-proBNP levels in the management of HFpEF patients in particular.

Project description:ImportanceAccurate risk prediction of morbidity and mortality in patients with heart failure with preserved ejection fraction (HFpEF) may help clinicians risk stratify and inform care decisions.ObjectiveTo develop and validate a novel prediction model for clinical outcomes in patients with HFpEF using routinely collected variables and to compare it with a biomarker-driven approach.Design, setting, and participantsData were used from the Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure (DELIVER) trial to derive the prediction model, and data from the Angiotensin Receptor Neprilysin Inhibition in Heart Failure With Preserved Ejection Fraction (PARAGON-HF) and the Irbesartan in Heart Failure With Preserved Ejection Fraction Study (I-PRESERVE) trials were used to validate it. The outcomes were the composite of HF hospitalization (HFH) or cardiovascular death, cardiovascular death, and all-cause death. A total of 30 baseline candidate variables were selected in a stepwise fashion using multivariable analyses to create the models. Data were analyzed from January 2023 to June 2023.ExposuresModels to estimate the 1-year and 2-year risk of cardiovascular death or hospitalization for heart failure, cardiovascular death, and all-cause death.ResultsData from 6263 individuals in the DELIVER trial were used to derive the prediction model and data from 4796 individuals in the PARAGON-HF trial and 4128 individuals in the I-PRESERVE trial were used to validate it. The final prediction model for the composite outcome included 11 variables: N-terminal pro-brain natriuretic peptide (NT-proBNP) level, HFH within the past 6 months, creatinine level, diabetes, geographic region, HF duration, treatment with a sodium-glucose cotransporter 2 inhibitor, chronic obstructive pulmonary disease, transient ischemic attack/stroke, any previous HFH, and heart rate. This model showed good discrimination (C statistic at 1 year, 0.73; 95% CI, 0.71-0.75) in both validation cohorts (C statistic at 1 year, 0.71; 95% CI, 0.69-0.74 in PARAGON-HF and 0.75; 95% CI, 0.73-0.78 in I-PRESERVE) and calibration. The model showed similar discrimination to a biomarker-driven model including high-sensitivity cardiac troponin T and significantly better discrimination than the Meta-Analysis Global Group in Chronic (MAGGIC) risk score (C statistic at 1 year, 0.60; 95% CI, 0.58-0.63; delta C statistic, 0.13; 95% CI, 0.10-0.15; P < .001) and NT-proBNP level alone (C statistic at 1 year, 0.66; 95% CI, 0.64-0.68; delta C statistic, 0.07; 95% CI, 0.05-0.08; P < .001). Models derived for the prediction of all-cause and cardiovascular death also performed well. An online calculator was created to allow calculation of an individual's risk.Conclusions and relevanceIn this prognostic study, a robust prediction model for clinical outcomes in HFpEF was developed and validated using routinely collected variables. The model performed better than NT-proBNP level alone. The model may help clinicians to identify high-risk patients and guide treatment decisions in HFpEF.

Dataset Information

First-Phase Ejection Fraction, a Measure of Preclinical Heart Failure, Is Strongly Associated With Increased Mortality in Patients With COVID-19.

Publications

First-Phase Ejection Fraction, a Measure of Preclinical Heart Failure, Is Strongly Associated With Increased Mortality in Patients With COVID-19.

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