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Heart Failure and Midrange Ejection Fraction: Implications of Recovered Ejection Fraction for Exercise Tolerance and Outcomes.

ABSTRACT: Evidence-based therapies for heart failure (HF) differ significantly according to left ventricular ejection fraction (LVEF). However, few data are available on the phenotype and prognosis of patients with HF with midrange LVEF of 40% to 55%, and the impact of recovered systolic function on the clinical features, functional capacity, and outcomes of this population is not known.We studied 944 patients with HF who underwent clinically indicated cardiopulmonary exercise testing. The study population was categorized according to LVEF as follows: HF with reduced LVEF (HFrEF; LVEF<40%; n=620); HF with midrange ejection fraction and no recovered ejection fraction (LVEF was consistent between 40% and 55%; n=107); HF with recovered midrange ejection fraction (LVEF, 40%-55% but previous LVEF<40%; n=170); and HF with preserved LVEF (HFpEF; LVEF>55%; n=47). HF with midrange ejection fraction and no recovered ejection fraction and HF with recovered midrange ejection fraction had similar clinical characteristics, which were intermediate between those of HFrEF and HFpEF, and comparable values of predicted peak oxygen consumption and minute-ventilation/carbon dioxide production slope, which were better than HFrEF and similar to HFpEF. After a median of 4.4 (2.9-5.7) years, there were 253 composite events (death, left ventricular assistant device implantation, or transplantation). In multivariable Cox-regression analysis, HF with recovered midrange ejection fraction had lower risk of composite events than HFrEF (hazard ratio, 0.25; 95% confidence interval, 0.13-0.47) and HF with midrange ejection fraction and no recovered ejection fraction (hazard ratio, 0.31; 95% confidence interval, 0.15-0.67), and similar prognosis when compared with HFpEF. In contrast, HF with midrange ejection fraction and no recovered ejection fraction tended to show intermediate risk of outcomes in comparison with HFpEF and HFrEF, albeit not reaching statistical significance in fully adjusted analyses.Patients with HF with midrange LVEF demonstrate a distinct clinical profile from HFpEF and HFrEF patients, with objective measures of functional capacity similar to HFpEF. Within the midrange LVEF HF population, recovered systolic function is a marker of more favorable prognosis.

SUBMITTER: Nadruz W

PROVIDER: S-EPMC4807736 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

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Heart Failure and Midrange Ejection Fraction: Implications of Recovered Ejection Fraction for Exercise Tolerance and Outcomes.

Nadruz Wilson W West Erin E Santos Mário M Skali Hicham H Groarke John D JD Forman Daniel E DE Shah Amil M AM

Circulation. Heart failure 20160401 4

<h4>Background</h4>Evidence-based therapies for heart failure (HF) differ significantly according to left ventricular ejection fraction (LVEF). However, few data are available on the phenotype and prognosis of patients with HF with midrange LVEF of 40% to 55%, and the impact of recovered systolic function on the clinical features, functional capacity, and outcomes of this population is not known.<h4>Methods and results</h4>We studied 944 patients with HF who underwent clinically indicated cardio ...[more]

PMID: 27009553

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Project description:Aims: Evidence-based guidelines for heart failure management depend mainly on current left ventricular ejection fraction (LVEF). However, fewer studies have examined the impact of prior LVEF. Patients may enter the heart failure with midrange ejection fraction (HFmrEF) category when heart failure with preserved ejection fraction (HFpEF) deteriorates or heart failure with reduced ejection fraction (HFrEF) improves. In this study, we examined the association between change in LVEF and adverse outcomes. Methods: HFmrEF patients with at least two or more echocardiograms 3 months apart at the First Affiliated Hospital of Dalian Medical University between September 1, 2015 and November 30, 2019 were identified. According to the prior LVEF, the subjects were divided into improved group (prior LVEF < 40%), stable group (prior LVEF between 40 and 50%), and deteriorated group (prior LVEF ≥ 50%). The primary outcomes were cardiovascular death, all-cause mortality, hospitalization for worsening heart failure, and composite event of all-cause mortality or all-cause hospitalization. Results: A total of 1,168 HFmrEF patients (67.04% male, mean age 63.60 ± 12.18 years) were included. The percentages of improved, stable, and deteriorated group were 310 (26.54%), 334 (28.60%), and 524 (44.86%), respectively. After a period of follow-up, 208 patients (17.81%) died and 500 patients met the composite endpoint. The rates of all-cause mortality were 35 (11.29%), 55 (16.47%), and 118 (22.52%), and the composite outcome was 102 (32.90%), 145 (43.41%), and 253 (48.28%) for the improved, stable, and deteriorated groups, respectively. Cox regression analysis showed that the deterioration group had higher risk of cardiovascular death (HR: 1.707, 95% CI: 1.064-2.739, P = 0.027), all-cause death (HR 1.948, 95% CI 1.335-2.840, P = 0.001), and composite outcome (HR 1.379, 95% CI 1.096-1.736, P = 0.006) compared to the improvement group. The association still remained significant after fully adjusted for both all-cause mortality (HR = 1.899, 95% CI 1.247-2.893, P = 0.003) and composite outcome (HR: 1.324, 95% CI: 1.020-1.718, P = 0.035). Conclusion: HFmrEF patients are heterogeneous with three different subsets identified, each with different outcomes. Strategies for managing HFmrEF should include previously measured LVEF to allow stratification based on direction changes in LVEF to better optimize treatment.

Project description:ImportancePatients categorized as having heart failure (HF) with left ventricular ejection fraction (LVEF) in the midrange between 40% and 50% (HFmrEF) are known to be at increased risk of future events. Although patients can transition into the midrange through either improvement or deterioration in their LVEF, there is limited information available assessing the association of directional change in LVEF with future events. Understanding the association between change in LVEF and the clinical course of patients with HFmrEF would be of value in guiding management strategies.ObjectiveTo determine whether risk of clinical events experienced by patients with HFmrEF varies according to whether LVEF improved or deteriorated into the range of 40% to 50% from previous measurements.Design, setting, and participantsIn this retrospective cohort study, patients were identified from the electronic health records at the UC San Diego Health System who had an LVEF measured between 40% and 50% on transthoracic echocardiography (TTE) performed during the calendar year of 2015 and who also had at least 1 prior TTE for comparison. The clinical course of these patients was then followed from the time of the index TTE through December 2018. Data were analyzed from January to March 2019.Main outcomes and measuresThe composite of all-cause mortality and all-cause hospitalization, the composite of cardiovascular mortality and HF hospitalization, and each of the individual components.ResultsOf the 448 patients who were identified with HFmrEF, 278 (62.1%) were male, and the mean (SD) age was 67.4 (9.7) years. Left ventricular ejection fraction improved from less than 40% in 157 patients (35.0%), deteriorated from greater than 50% in 224 patients (50.0%), and remained between 40% and 50% over time in 67 patients (15.0%). Compared with patients whose LVEF improved from less than 40% to midrange levels, patients whose LVEF deteriorated from greater than 50% had higher risk of all-cause mortality and hospitalization (hazard ratio, 1.34; 95% CI, 1.10-1.82; P = .03) and of cardiovascular mortality and HF hospitalization (hazard ratio, 1.71; 95% CI, 1.08-2.50; P = .02), and these differences persisted after multivariable analysis. Outcomes did not differ significantly between patients whose LVEF improved and those in whom it remained stable.Conclusion and relevanceIn a cohort of patients with HFmrEF from a large academic medical center, the clinical course was strongly influenced by the directional change in LVEF from prior study. Patients whose LVEF deteriorated into midrange levels experienced a significantly higher risk of adverse clinical events than patients whose LVEF had improved. These results suggest that directional change in LVEF from prior measurements should be considered when devising management strategies for patients with HFmrEF.

Project description:BACKGROUND:This study aimed to compare the independent and incremental prognostic value of peak oxygen consumption (VO2) and minute ventilation/carbon dioxide production (VE/VCO2) in heart failure (HF) with preserved (HFpEF), midrange (HFmEF), and reduced (HFrEF) ejection fraction (LVEF). METHODS AND RESULTS:In 195 HFpEF (LVEF ?50%), 144 HFmEF (LVEF 40-49%), and 630 HFrEF (LVEF <40%) patients, we assessed the association of cardiopulmonary exercise testing variables with the composite outcome of death, left ventricular assist device implantation, or heart transplantation (256 events; median follow-up of 4.2 years), and 2-year incident HF hospitalization (244 events). In multivariable Cox regression analysis, greater association with outcomes in HFpEF than HFrEF were noted with peak VO2 (HR [95% confidence interval]: 0.76 [0.67-0.87] versus 0.87 [0.83-0.90] for the composite outcome, Pinteraction=0.052; 0.77 [0.69-0.86] versus 0.92 [0.88-0.95], respectively for HF hospitalization, Pinteraction=0.003) and VE/VCO2 slope (1.11 [1.06-1.17] versus 1.04 [1.03-1.06], respectively for the composite outcome, Pinteraction=0.012; 1.10 [1.05-1.15] versus 1.04 [1.03-1.06], respectively for HF hospitalization, Pinteraction=0.019). In HFmEF, peak VO2 and VE/VCO2 slope were associated with the composite outcome (0.79 [0.70-0.90] and 1.12 [1.05-1.19], respectively), while only peak VO2 was related to HF hospitalization (0.81 [0.72-0.92]). In HFpEF and HFrEF, peak VO2 and VE/VCO2 slope provided incremental prognostic value beyond clinical variables based on the C-statistic, net reclassification improvement, and integrated diagnostic improvement, with models containing both measures demonstrating the greatest incremental value. CONCLUSIONS:Both peak VO2 and VE/VCO2 slope provided incremental value beyond clinical characteristics and LVEF for predicting outcomes in HFpEF. Cardiopulmonary exercise testing variables provided greater risk discrimination in HFpEF than HFrEF.

Project description:AimsVisceral adipose tissue (AT) promotes inflammation and may be associated with disease progression in heart failure with preserved ejection fraction (HFpEF). We characterized regional AT distribution in HFpEF patients and controls and analysed associations with co-morbidities and exercise tolerance.Methods and resultsMagnetic resonance imaging was performed to quantify epicardial, liver, abdominal, and thigh skeletal muscle AT. We assessed New York Heart Association (NYHA) class, 6 min walk distance, and global well-being score. Multivariable linear regression models adjusting for body surface area were used. We studied 55 HFpEF patients (41 women, mean age 67 ± 11 years) and 33 controls (21 women, mean age 57 ± 10 years). Epicardial AT (median [interquartile range] 4.6 [2.0] vs. 3.2 [1.4] mm, P < 0.001), thigh intermuscular fat (11.0 [11.5] vs. 5.0 [2.7] cm2 , P < 0.001) and liver fat fraction (6.4% [6.1] vs. 4.1% [5.5], P = 0.001) were higher in HFpEF patients than controls. Women with HFpEF had higher abdominal and thigh subcutaneous AT than men. Greater thigh intermuscular fat was associated with higher blood pressure (β [SE] 0.73 [0.17], P < 0.001) and diabetes (odds ratio [95% confidence interval] 1.2 [1.0-1.5], P = 0.03). Greater thigh intramuscular fat was associated with both worse NYHA class (β [SE] 2.7 [1.0], P = 0.01) and shorter 6 min walk distance (β [SE] -4.1 [1.9], P = 0.03), and greater epicardial AT (β [SE] -0.2 [0.1], P < 0.001) and liver fat fraction (β [SE] -0.4 [0.2], P = 0.04) were associated with lower global well-being score.ConclusionsHeart failure with preserved ejection fraction patients have increased epicardial, liver, and skeletal muscle fat compared with controls out of proportion to their increased body size, and adiposity was associated with worse NYHA class and exercise tolerance in HFpEF. These results provide the basis for further investigation into the effect of interventions to reduce regional AT distribution in relation to HFpEF symptoms and pathophysiology.

Project description:Importance:Despite intensive treatment, hospitalized patients with acute decompensated heart failure (ADHF) have a substantial risk of postdischarge mortality. Limited data are available on the possible differences in the incidence and mechanisms of death among patients with heart failure with reduced ejection fraction (HFrEF), heart failure with midrange ejection fraction (HFmrEF), and heart failure with preserved ejection fraction (HFpEF). Objectives:To examine the incidences and mode of postdischarge mortality among patients with ADHF and to compare the risk profile among patients with HFrEF, HFmrEF, and HFpEF. Design, Setting, and Participants:This prospective cohort study of 4056 patients hospitalized for ADHF analyzed data from 3717 patients who were discharged from October 1, 2014, to March 31, 2016. Data analysis was performed from April 1 to August 31, 2019. Exposures:Death among patients with ADHF after hospital discharge. Main Outcomes and Measures:All-cause death and cause of postdischarge mortality after the index hospitalization by left ventricular ejection fraction (LVEF) subgroup. Results:A total of 3717 patients (mean [SD] age, 77.7 [12.0] years; 2049 [55.1%] male) were included in the study. The mean (SD) LVEF at baseline was 46.4%?(16.2%). Among 3717 enrolled patients, 1383 (37.2%) were categorized as having HFrEF (LVEF, <40%), 703 (18.9%) as having HFmrEF (LVEF, 40%-49%), and 1631 (43.9%) as having HFpEF (LVEF, ?50%). The incidence and causes of death were evaluated after discharge from the index hospitalization. The median follow-up period was 470 days (interquartile range, 357-649 days), and the 1-year follow-up rate was 96%. During follow-up, all-cause death occurred in 848 patients (22.8%; HFrEF group: 298 [21.5%; 95% CI, 19.5%-23.8%]; HFmrEF group: 158 [22.5%; 95% CI, 19.5%-25.7%]; and HRpEF group: 392 [24.0%; 95% CI, 22.0%-26.2%]; P?=?.26), cardiovascular deaths occurred in 523 patients (14.1%; HFrEF group: 203 [14.7%; 95% CI, 12.9%-16.6%]; HFmrEF group: 97 [13.8%; 95% CI, 11.4%-16.5%]; and HFpEF group: 223 [13.7%; 95% CI, 12.1%-15.4%]; P?=?.71), and sudden cardiac death occurred in 98 patients (2.6%; HFrEF group: 44 [3.2%; 95% CI, 2.4%-4.2%]; HFmrEF group: 14 [2.0%; 95% CI, 1.2%-3.3%]; and HFpEF group: 40 [2.5%; 95% CI, 1.8%-3.3%]; P?=?.23). The risks of causes of death were similar among the subtypes. Conclusions and Relevance:The mode of death was similar among the heart failure subtypes. Given the nonnegligible incidence of sudden cardiac death in patients with HFpEF found in this study, further studies appear to be warranted to identify a high-risk subset in this population.

Dataset Information

Heart Failure and Midrange Ejection Fraction: Implications of Recovered Ejection Fraction for Exercise Tolerance and Outcomes.

Publications

Heart Failure and Midrange Ejection Fraction: Implications of Recovered Ejection Fraction for Exercise Tolerance and Outcomes.

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