Unsupervised cluster analysis of patients with recovered left ventricular ejection fraction identifies unique clinical phenotypes.
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ABSTRACT: Background
Patients with heart failure (HF) with recovered ejection fraction (HFrecEF) are a recently identified cohort that are phenotypically and biologically different from HFrEF and HFpEF patients. Whether there are unique phenotypes among HFrecEF patients is not known.Methods
We studied all patients at a large medical center, who had an improvement in LVEF from ≤ 35% to ≥ 50% (LVrecEF) between January 1, 2005 and December 31, 2013. We identified a set of 11 clinical variables and then performed unsupervised clustering analyses to identify unique clinical phenotypes among patients with LVrecEF, followed by a Kaplan-Meier analysis to identify differences in survival and the proportion of LVrecEF patients who maintained an LVEF ≥ 50% during the study period.Results
We identified 889 patients with LVrecEF who clustered into 7 unique phenotypes ranging in size from 37 to 420 patients. Kaplan-Meier analysis demonstrated significant differences in mortality across clusters (logrank p<0.0001), with survival ranging from 14% to 87% at 1000 days, as well as significant differences in the proportion of LVrecEF patients who maintained an LVEF ≥ 50%.Conclusion
There is significant clinical heterogeneity among patients with LVrecEF. Clinical outcomes are distinct across phenotype clusters as defined by clinical cardiac characteristics and co-morbidities. Clustering algorithms may identify patients who are at high risk for recurrent HF, and thus be useful for guiding treatment strategies for patients with LVrecEF.
SUBMITTER: Perry A
PROVIDER: S-EPMC7971566 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Patients with recovery of left ventricular ejection fraction (LVEF) remain at risk for future deterioration of LVEF. However, there are no tools to risk stratify these patients. We hypothesized that global longitudinal strain (GLS) could predict sustained recovery within this population. We retrospectively identified 96 patients with a reduced LVEF <50% (screening echocardiogram), whose LVEF had increased by at least 10% and normalized (>50%) on evidence-based medical therapies (baseline echocardiogram). We examined absolute GLS on the baseline echocardiogram in relation to changes in LVEF on a follow-up echocardiogram. Patients with recovered LVEF had a wide range of GLS. The GLS on the baseline study correlated with the LVEF at the time of follow-up (r=0.33; P<0.001). The likelihood of having an LVEF >50% on follow-up increased by 24% for each point increase in absolute GLS on the baseline study (odds ratio, 1.24; P=0.001). An abnormal GLS (≤16%) at baseline had a sensitivity of 88%, a specificity of 46%, and an accuracy of 0.67 (P<0.001) as a predictor of a decrease in LVEF >5% during follow-up. A normal GLS (>16%) on the baseline study had a sensitivity of 47%, a specificity of 83%, and an accuracy of 0.65 (P=0.002) for predicting a stable LVEF (-5% to 5%) on follow-up. In patients with a recovered LVEF, an abnormal GLS predicts the likelihood of having a decreased LVEF during follow-up, whereas a normal GLS predicts the likelihood of stable LVEF during recovery.
| S-EPMC5505492 | biostudies-literature
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.
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Project description:This study sought to examine the association of a borderline left ventricular ejection fraction (LVEF) of 50% to 55% with cardiovascular morbidity and mortality in a community-based cohort.Guidelines stipulate a LVEF >55% as normal, but the optimal threshold, if any, remains uncertain. The prognosis of a "borderline" LVEF, 50% to 55%, is unknown.This study evaluated Framingham Heart Study participants who underwent echocardiography between 1979 and 2008 (n = 10,270 person-observations, mean age 60 years, 57% women). Using pooled data with up to 12 years of follow-up and multivariable Cox regression, we evaluated the associations of borderline LVEF and continuous LVEF with the risk of developing a composite outcome (heart failure [HF] or death; primary outcome) and incident HF (secondary outcome).During follow-up (median 7.9 years), HF developed in 355 participants, and 1,070 died. Among participants with an LVEF of 50% to 55% (prevalence 3.5%), rates of the composite outcome and HF were 0.24 and 0.13 per 10 years of follow-up, respectively, versus 0.16 and 0.05 in participants having a normal LVEF. In multivariable-adjusted analyses, LVEF of 50% to 55% was associated with increased risk of the composite outcome (hazard ratio [HR]: 1.37; 95% confidence interval [CI]: 1.05 to 1.80) and HF (HR: 2.15; 95% CI: 1.41 to 3.28). There was a linear inverse relationship of continuous LVEF with the composite outcome (HR per 5 LVEF% decrement: 1.12; 95% CI: 1.07 to 1.16) and HF (HR per 5 LVEF% decrement: 1.23; 95% CI: 1.15 to 1.32).Persons with an LVEF of 50% to 55% in the community have greater risk for morbidity and mortality relative to persons with an LVEF >55%. Additional studies are warranted to elucidate the optimal management of these individuals.
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Project description:BackgroundStatins taken for cardiovascular indications by patients with breast cancer and lymphoma during doxorubicin treatment may attenuate left ventricular ejection fraction (LVEF) decline, but the effect of statins on LVEF among patients with no cardiovascular indications is unknown.MethodsA double-blind, placebo-controlled, 24-month randomized trial of 40 mg of atorvastatin per day administered to patients with breast cancer and lymphoma receiving doxorubicin was conducted within the National Cancer Institute Community Oncology Research Program across 31 sites in the United States. At pretreatment and then 6 and 24 months after initiating doxorubicin, we assessed left ventricular (LV) volumes, strain, mass, and LVEF through cardiac magnetic resonance imaging, along with cognitive function and serum markers of inflammation. The primary outcome was the difference in 24-month LVEF between placebo and treatment groups, adjusted for pretreatment LVEF.ResultsA total of 279 participants were enrolled in the trial. Participants had a mean (±SD) age of 49±12 years; 92% were women; and 83% were White. The mean (±SD) LVEF values were 61.7±5.5% before treatment and 57.4±6.8% at 24 months in the placebo group and 62.6±6.4% before treatment and 57.7±5.6% at 24 months in the atorvastatin group. On the basis of a multiple imputed data set for missing data and adjusted for each individual's pretreatment LVEF, 24-month declines in LVEF averaged 3.3±0.6 percentage points and 3.2±0.7 percentage points, for those randomly assigned to placebo versus statins, respectively (P=0.93). Across both treatment arms, similar percentages of individuals experienced changes of more than 10 percentage points in LVEF, LV strain, LV mass, cognition, and inflammation biomarkers, including among those with greater than 90% drug compliance.ConclusionsIn patients with breast cancer and lymphoma with no existing indication for statin therapy, prospective statin administration did not affect LVEF declines 2 years after doxorubicin. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT01988571.).
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Project description:BackgroundLeft ventricular ejection fraction (EF) is an indicator of cardiac function, usually assessed in individuals with heart failure and other cardiac conditions. Although family studies indicate that EF has an important genetic component with heritability estimates up to 0.61, to date only 6 EF-associated loci have been reported.MethodsHere, we conducted a genome-wide association study (GWAS) of EF in 26 638 adults from the Genetic Epidemiology Research on Adult Health and Aging and the UK Biobank cohorts.ResultsA meta-analysis combining results from Genetic Epidemiology Research on Adult Health and Aging and UK Biobank identified a novel locus: TMEM40 on chromosome 3p25 (rs11719526; β=0.47 and P=3.10×10-8) that replicated in Biobank Japan and confirmed recent findings implicating the BAG3 locus on chromosome 10q26 in EF variation, with the strongest association observed for rs17617337 (β=-0.83 and P=8.24×10-17). Although the minor allele frequencies of TMEM40 rs11719526 were generally common (between 0.13 and 0.44) in different ethnic groups, BAG3 rs17617337 was rare (minor allele frequencies<0.05) in Asian and African ancestry populations. These associations were slightly attenuated, after considering antecedent cardiac conditions (ie, heart failure/cardiomyopathy, hypertension, myocardial infarction, atrial fibrillation, valvular disease, and revascularization procedures). This suggests that the effects of the lead variants at TMEM40 or BAG3 on EF are largely independent of these conditions.ConclusionsIn this large and multiethnic study, we identified 2 loci, TMEM40 and BAG3, associated with EF at a genome-wide significance level. Identifying and understanding the genetic determinants of EF is important to better understand the pathophysiology of this strong correlate of cardiac outcomes and to help target the development of future therapies.
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Project description:BackgroundThe right ventricle (RV) in hypertrophic cardiomyopathy (HCM) tends to be neglected, as previous efforts have predominantly focused on examining the prognostic value of left ventricular (LV) abnormalities. The objectives of this study were to assess RV function in HCM, changes over time, and association with clinical outcomes.MethodsTwo hundred and ninety HCM patients with preserved LV ejection fraction (LVEF ≥ 55%) and 30 age- and sex-matched controls underwent cardiovascular magnetic resonance (CMR). All patients were followed up for clinical events for a median duration of 4.4 years. Sixty-three patients had a follow-up CMR undertaken at a median interval of 5.4 years. Main study measures and outcomes were RV function (RV ejection fraction (RVEF) and RV strain) at baseline, temporal changes in RV function over time and prognostic value of RV dysfunction for predicting cardiovascular outcomes in HCM.ResultsWhen compared to controls, HCM patients exhibited lower RV and LV peak global longitudinal systolic strains on feature-tracking analysis of cine images, while RVEF and LVEF were within the normal range. On follow-up CMR, both RV and LV strain parameters decreased over time. RVEF decreased at follow-up (65 ± 7% to 62 ± 7%, P < 0.001) but the change in LVEF was not significant (68 ± 10% to 66 ± 8%, P = 0.30). On clinical follow up, reduced RVEF was an independent predictor of non-sustained ventricular tachycardia (NSVT) [HR 1.10 (95% CI 1.06-1.15), P < 0.001] and composite cardiovascular events (NSVT, stroke, heart failure hospitalisation and cardiovascular death) [HR 1.07 (95% CI 1.03-1.10), P < 0.001]. RV longitudinal strain was an independent predictor of NSVT [HR 1.05 (95% CI 1.01-1.09), P = 0.029]. Patients with RVEF < 55% showed an increased risk of NSVT and composite cardiovascular events. In contrast, LVEF and LV global longitudinal strain were not predictive of such events on multivariable analysis.ConclusionsIn HCM, RV function, including RV strain, and LV strain decrease over time despite preserved LVEF. Reduction in RV but not LV function is associated with adverse cardiovascular outcomes. Assessing RV function in early HCM disease might have a role in risk stratification to prevent future cardiovascular events.
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Project description:Nonischemic cardiomyopathy is a common cause of left ventricular (LV) dysfunction and myocardial fibrosis. The purpose of this study was to noninvasively evaluate changes in segmental LV extracellular volume (ECV) fraction, LV velocities, myocardial scar, and wall motion in nonischemic cardiomyopathy patients.Cardiac MRI including pre- and postcontrast myocardial T1 mapping and velocity quantification (tissue phase mapping) of the LV (basal, midventricular, and apical short axis) was applied in 31 patients with nonischemic cardiomyopathy (50±18 years). Analysis based on the 16-segment American Heart Association model was used to evaluate the segmental distribution of ECV, peak systolic and diastolic myocardial velocities, scar determined by late gadolinium enhancement, and wall motion abnormalities. LV segments with scar or impaired wall motion were significantly associated with elevated ECV (rs =0.26; P<0.001) and reduced peak systolic radial velocities (r=-0.43; P<0.001). Regional myocardial velocities and ECV were similar for patients with reduced (n=12; ECV=0.28±0.06) and preserved left ventricular ejection fraction (n=19; ECV=0.30±0.09). Patients with preserved left ventricular ejection fraction showed significant relationships between increasing ECV and reduced systolic (r=-0.19; r=-0.30) and diastolic (r=0.34; r=0.26) radial and long-axis peak velocities (P<0.001). Even after excluding myocardial segments with late gadolinium enhancement, significant relationships between ECV and segmental LV velocities were maintained indicating the potential of elevated ECV to identify regional diffuse fibrosis not visible by late gadolinium enhancement, which was associated with impaired regional LV function.Regionally elevated ECV negatively affected myocardial velocities. The association of elevated regional ECV with reduced myocardial velocities independent of left ventricular ejection fraction suggests a structure-function relationship between altered ECV and segmental myocardial function in nonischemic cardiomyopathy.
| S-EPMC4283574 | biostudies-literature
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.
| S-EPMC7301304 | biostudies-literature
Project description:ObjectiveRecent studies have reported suboptimal up-titration of heart failure (HF) therapies in patients with heart failure and a reduced ejection fraction (HFrEF). Here, we report on the achieved doses after nurse-led up-titration, reasons for not achieving the target dose, subsequent changes in left ventricular ejection fraction (LVEF), and mortality.MethodsFrom 2012 to 2018, 378 HFrEF patients with a recent (< 3 months) diagnosis of HF were referred to a specialised HF-nurse led clinic for protocolised up-titration of guideline-directed medical therapy (GDMT). The achieved doses of GDMT at 9 months were recorded, as well as reasons for not achieving the optimal dose in all patients. Echocardiography was performed at baseline and after up-titration in 278 patients.ResultsOf 345 HFrEF patients with a follow-up visit after 9 months, 69% reached ≥ 50% of the recommended dose of renin-angiotensin-system (RAS) inhibitors, 73% reached ≥ 50% of the recommended dose of beta-blockers and 77% reached ≥ 50% of the recommended dose of mineralocorticoid receptor antagonists. The main reasons for not reaching the target dose were hypotension (RAS inhibitors and beta-blockers), bradycardia (beta-blockers) and renal dysfunction (RAS inhibitors). During a median follow-up of 9 months, mean LVEF increased from 27.6% at baseline to 38.8% at follow-up. Each 5% increase in LVEF was associated with an adjusted hazard ratio of 0.84 (0.75-0.94, p = 0.002) for mortality and 0.85 (0.78-0.94, p = 0.001) for the combined endpoint of mortality and/or HF hospitalisation after a mean follow-up of 3.3 years.ConclusionsThis study shows that protocolised up-titration in a nurse-led HF clinic leads to high doses of GDMT and improvement of LVEF in patients with new-onset HFrEF.
| S-EPMC8271074 | biostudies-literature