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      Frequency, predictors, and prognosis of ejection fraction improvement in heart failure: an echocardiogram-based registry study

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          Abstract

          Aims

          To identify variables predicting ejection fraction (EF) recovery and characterize prognosis of heart failure (HF) patients with EF recovery (HFrecEF).

          Methods and results

          Retrospective study of adults referred for ≥2 echocardiograms separated by ≥6 months between 2008 and 2016 at the two largest echocardiography centres in Alberta who also had physician-assigned diagnosis of HF. Of 10 641 patients, 3124 had heart failure reduced ejection fraction (HFrEF) (EF ≤ 40%) at baseline: while mean EF declined from 30.2% on initial echocardiogram to 28.6% on the second echocardiogram in those patients with persistent HFrEF (defined by <10% improvement in EF), it improved from 26.1% to 46.4% in the 1174 patients (37.6%) with HFrecEF (defined by EF absolute improvement ≥10%). On multivariate analysis, female sex [adjusted odds ratio (aOR) 1.66, 95% confidence interval (CI) 1.40–1.96], younger age (aOR per decade 1.16, 95% CI 1.09–1.23), atrial fibrillation (aOR 2.00, 95% CI 1.68–2.38), cancer (aOR 1.52, 95% CI 1.03–2.26), hypertension (aOR 1.38, 95% CI 1.18–1.62), lower baseline ejection fraction (aOR per 1% decrease 1.07 (1.06–1.08), and using hydralazine (aOR 1.69, 95% CI 1.19–2.40) were associated with EF improvements ≥10%. HFrecEF patients demonstrated lower rates per 1000 patient years of mortality (106 vs. 164, adjusted hazard ratio, aHR 0.70 [0.62–0.79]), all-cause hospitalizations (300 vs. 428, aHR 0.87 [0.79–0.95]), all-cause emergency room (ER) visits (569 vs. 799, aHR 0.88 [0.81–0.95]), and cardiac transplantation or left ventricular assist device implantation (2 vs. 10, aHR 0.21 [0.10–0.45]) compared to patients with persistent HFrEF. Females with HFrEF exhibited lower mortality risk (aHR 0.94 [0.88–0.99]) than males after adjusting for age, time between echocardiograms, clinical comorbidities, medications, and whether their EF improved or not during follow-up.

          Conclusion

          HFrecEF patients tended to be younger, female, and were more likely to have hypertension, atrial fibrillation, or cancer. HFrecEF patients have a substantially better prognosis compared to those with persistent HFrEF, even after multivariable adjustment, and female patients exhibit lower mortality risk than men within each subgroup (HFrecEF and persistent HFrEF) even after multivariable adjustment.

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          Most cited references27

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          Survival after the onset of congestive heart failure in Framingham Heart Study subjects.

          Relatively limited epidemiological data are available regarding the prognosis of congestive heart failure (CHF) and temporal changes in survival after its onset in a population-based setting. Proportional hazards models were used to evaluate the effects of selected clinical variables on survival after the onset of CHF among 652 members of the Framingham Heart Study (51% men; mean age, 70.0 +/- 10.8 years) who developed CHF between 1948 and 1988. Subjects were older at the diagnosis of heart failure in the later decades of this study (mean age at heart failure diagnosis, 57.3 +/- 7.6 years in the 1950s, 65.9 +/- 7.9 years in the 1960s, 71.6 +/- 9.4 years in the 1970s, and 76.4 +/- 10.0 years in the 1980s; p < 0.001). Median survival after the onset of heart failure was 1.7 years in men and 3.2 years in women. Overall, 1-year and 5-year survival rates were 57% and 25% in men and 64% and 38% in women, respectively. Survival was better in women than in men (age-adjusted hazards ratio for mortality, 0.64; 95% CI, 0.54-0.77). Mortality increased with advancing age in both sexes (hazards ratio for men, 1.27 per decade of age; 95% CI, 1.09-1.47; hazards ratio for women, 1.61 per decade of age; 95% CI, 1.37-1.90). Adjusting for age, there was no significant temporal change in the prognosis of CHF during the 40 years of observation (hazards ratio for men for mortality, 1.08 per calendar decade; 95% CI, 0.92-1.27; hazards ratio for women for mortality, 1.02 per calendar decade; 95% CI, 0.83-1.26). CHF remains highly lethal, with better prognosis in women and in younger individuals. Advances in the treatment of hypertension, myocardial ischemia, and valvular heart disease during the four decades of observation did not translate into appreciable improvements in overall survival after the onset of CHF in this large, unselected population.
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            Withdrawal of pharmacological treatment for heart failure in patients with recovered dilated cardiomyopathy (TRED-HF): an open-label, pilot, randomised trial

            Summary Background Patients with dilated cardiomyopathy whose symptoms and cardiac function have recovered often ask whether their medications can be stopped. The safety of withdrawing treatment in this situation is unknown. Methods We did an open-label, pilot, randomised trial to examine the effect of phased withdrawal of heart failure medications in patients with previous dilated cardiomyopathy who were now asymptomatic, whose left ventricular ejection fraction (LVEF) had improved from less than 40% to 50% or greater, whose left ventricular end-diastolic volume (LVEDV) had normalised, and who had an N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) concentration less than 250 ng/L. Patients were recruited from a network of hospitals in the UK, assessed at one centre (Royal Brompton and Harefield NHS Foundation Trust, London, UK), and randomly assigned (1:1) to phased withdrawal or continuation of treatment. After 6 months, patients in the continued treatment group had treatment withdrawn by the same method. The primary endpoint was a relapse of dilated cardiomyopathy within 6 months, defined by a reduction in LVEF of more than 10% and to less than 50%, an increase in LVEDV by more than 10% and to higher than the normal range, a two-fold rise in NT-pro-BNP concentration and to more than 400 ng/L, or clinical evidence of heart failure, at which point treatments were re-established. The primary analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT02859311. Findings Between April 21, 2016, and Aug 22, 2017, 51 patients were enrolled. 25 were randomly assigned to the treatment withdrawal group and 26 to continue treatment. Over the first 6 months, 11 (44%) patients randomly assigned to treatment withdrawal met the primary endpoint of relapse compared with none of those assigned to continue treatment (Kaplan-Meier estimate of event rate 45·7% [95% CI 28·5–67·2]; p=0·0001). After 6 months, 25 (96%) of 26 patients assigned initially to continue treatment attempted its withdrawal. During the following 6 months, nine patients met the primary endpoint of relapse (Kaplan-Meier estimate of event rate 36·0% [95% CI 20·6–57·8]). No deaths were reported in either group and three serious adverse events were reported in the treatment withdrawal group: hospital admissions for non-cardiac chest pain, sepsis, and an elective procedure. Interpretation Many patients deemed to have recovered from dilated cardiomyopathy will relapse following treatment withdrawal. Until robust predictors of relapse are defined, treatment should continue indefinitely. Funding British Heart Foundation, Alexander Jansons Foundation, Royal Brompton Hospital and Imperial College London, Imperial College Biomedical Research Centre, Wellcome Trust, and Rosetrees Trust.
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              Methods for identifying 30 chronic conditions: application to administrative data

              Background Multimorbidity is common and associated with poor clinical outcomes and high health care costs. Administrative data are a promising tool for studying the epidemiology of multimorbidity. Our goal was to derive and apply a new scheme for using administrative data to identify the presence of chronic conditions and multimorbidity. Methods We identified validated algorithms that use ICD-9 CM/ICD-10 data to ascertain the presence or absence of 40 morbidities. Algorithms with both positive predictive value and sensitivity ≥70% were graded as “high validity”; those with positive predictive value ≥70% and sensitivity <70% were graded as “moderate validity”. To show proof of concept, we applied identified algorithms with high to moderate validity to inpatient and outpatient claims and utilization data from 574,409 people residing in Edmonton, Canada during the 2008/2009 fiscal year. Results Of the 40 morbidities, we identified 30 that could be identified with high to moderate validity. Approximately one quarter of participants had identified multimorbidity (2 or more conditions), one quarter had a single identified morbidity and the remaining participants were not identified as having any of the 30 morbidities. Conclusions We identified a panel of 30 chronic conditions that can be identified from administrative data using validated algorithms, facilitating the study and surveillance of multimorbidity. We encourage other groups to use this scheme, to facilitate comparisons between settings and jurisdictions. Electronic supplementary material The online version of this article (doi:10.1186/s12911-015-0155-5) contains supplementary material, which is available to authorized users.
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                Author and article information

                Journal
                European Heart Journal
                Oxford University Press (OUP)
                0195-668X
                1522-9645
                July 07 2019
                July 07 2019
                April 25 2019
                July 07 2019
                July 07 2019
                April 25 2019
                : 40
                : 26
                : 2110-2117
                Affiliations
                [1 ]Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada
                [2 ]Department of Cardiac Sciences, University of Calgary and Libin Cardiovascular Institute of Alberta, Calgary, AB, Canada
                [3 ]Faculty of Medicine and Dentistry, University of Alberta Canadian VIGOUR Center, University of Alberta, Edmonton, AB, Canada
                [4 ]Data Platform, Alberta Strategy for Patient Oriented Research Support Unit, Edmonton, AB, Canada
                [5 ]Division of General Internal Medicine, University of Alberta, Edmonton, AB, Canada
                Article
                10.1093/eurheartj/ehz233
                31280320
                791beb91-e66d-4f4d-97ed-6005f84a750e
                © 2019

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