Dataset Information

Long-Term Outcomes of Adults With Heart Failure by Left Ventricular Systolic Function Status.

ABSTRACT: Patients with heart failure (HF) and preserved (HFpEF) or borderline preserved ejection fraction (HFbEF) outnumber patients with HF and reduced ejection fraction (HFrEF), but limited data exist on outcomes in community-based populations of these patients. We examined clinical outcomes in a diverse population of adults with HFrEF, HFbEF, and HFpEF. All adults with diagnosed HF from 2005 to 2012 in Kaiser Permanente Northern California were categorized by left ventricular systolic function as HFpEF (EF ?50%), HFbEF (EF 41-49%), or HFrEF (EF ?40%). Demographics, clinical characteristics, and therapies were obtained from electronic records. Outcomes included death, HF hospitalization, and HF-related emergency department (ED) visit. In 28,914 eligible HF patients, there were 52% HFpEF, 16% HFbEF, and 32% HFrEF, with mean age 72.8 years and 45% women. During median follow-up of 3.5 years, crude rates (per 100 person-years) of death, HF hospitalization, and HF-related ED visit were 14.5 (95% CI 14.3 to 14.7), 15.8 (15.5 to 16.0), and 38.2 (37.8 to 38.5), respectively. Compared with HFrEF patients, adjusted hazard ratios of death, HF hospitalization, and HF-related ED visit for HFpEF patients were 0.82 (0.79 to 0.85), 0.72 (0.68 to 0.75), and 0.94 (0.90 to 0.99), respectively, and for HFbEF patients were 0.84 (0.79 to 0.88), 0.79 (0.73 to 0.84), and 0.90 (0.84 to 0.96), respectively. In conclusion, within a large community-based HF cohort, adjusted rates of death, HF hospitalization, and HF-related ED visits were similar in HFpEF and HFbEF patients, but higher in HFrEF patients. Regardless of systolic function, however, long-term mortality and morbidity in all HF patients remain high, reinforcing the need for novel strategies to improve long-term outcomes.

SUBMITTER: Avula HR

PROVIDER: S-EPMC6740246 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Long-Term Outcomes of Adults With Heart Failure by Left Ventricular Systolic Function Status.

Avula Harshith R HR Leong Thomas K TK Lee Keane K KK Sung Sue Hee SH Go Alan S AS

The American journal of cardiology 20180621 6

Patients with heart failure (HF) and preserved (HFpEF) or borderline preserved ejection fraction (HFbEF) outnumber patients with HF and reduced ejection fraction (HFrEF), but limited data exist on outcomes in community-based populations of these patients. We examined clinical outcomes in a diverse population of adults with HFrEF, HFbEF, and HFpEF. All adults with diagnosed HF from 2005 to 2012 in Kaiser Permanente Northern California were categorized by left ventricular systolic function as HFpE ...[more]

PMID: 30057237

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Project description:BackgroundAnemia is associated with decreased functional capacity, reduced quality of life, and worsened outcomes among patients with heart failure (HF) due to reduced left ventricular ejection fraction (HFREF). We sought to evaluate the independent effect of anemia on clinical outcomes among those with HFREF.HypothesisAnemia is associated with cardiovascular events in patients with heart failure.MethodsThe HF-ACTION trial was a prospective, randomized trial of exercise therapy vs usual care in 2331 patients with HFREF. Patients with New York Heart Association class II to IV HF and left ventricular ejection fractions of ≤ 35% were recruited. Hemoglobin (Hb) was measured up to 1 year prior to entry and was stratified by quintile. Anemia was defined as baseline Hb <13 g/dL and <12 g/dL in men and women, respectively. Hemoglobin was assessed in 2 models: a global prediction model that had been previously developed, and a modified model including variables associated with anemia and the studied outcomes.ResultsHemoglobin was available at baseline in 1763 subjects (76% of total study population); their median age was 59.0 years, 73% were male, and 62% were Caucasian. The prevalence of anemia was 515/1763 (29%). Older age, female sex, African American race, diabetes, hypertension, and lower estimated glomerular filtration rates were all more frequent in lower Hb quintiles. Over a median follow-up of 30 months, the primary outcome of all-cause mortality or all-cause hospitalization occurred in 78% of those with anemia and 64% in those without (P < 0.001). The secondary outcomes of all-cause mortality alone,cardiovascular (CV) mortality or CV hospitalization, and CV mortality or HF hospitalization occurred in 23% vs 15%, 67% vs 54%, and 44 vs 29%, respectively (P < 0.001). Heart failure hospitalizations occurred in 36% vs 22%, and urgent outpatient visits for HF exacerbations occurred in 67% and 55%, respectively (P < 0.001). For the global model, there was an association observed for anemia and all-cause mortality or hospitalization (adjusted hazard ratio [HR]: 1.15, 95% confidence interval [CI]: 1.01-1.32, P = 0.04), but other outcomes were not significant at P < 0.05. In the modified model, the adjusted HR for anemia and the primary outcome of all-cause mortality or all-cause hospitalization was 1.25 (95% CI: 1.10-1.42, P < 0.001). There were independent associations between anemia and all-cause death (HR: 1.11, 95% CI: 0.87-1.42, P = 0.38), CV death or CV hospitalization (HR: 1.16, 95% CI: 1.01-1.33, P = 0.035), and CV death and HF hospitalization (HR: 1.27, 95% CI: 1.06-1.51, P = 0.008).ConclusionsAnemia modestly is associated with increased rates of death, hospitalization, and HF exacerbation in patients with chronic HFREF. After adjusting for other important covariates, anemia is independently associated with an excess hazard for all-cause mortality and all-cause hospitalization. Anemia is also associated with combinations of CV death and CV/HF hospitalizations as composite endpoints.

Project description:Heart failure due to chronic volume overload (VO) in rats and humans is characterized by disorganization of the cardiomyocyte desmin/mitochondrial network. Here, we tested the hypothesis that desmin breakdown is an early and continuous process throughout VO. Male Sprague-Dawley rats had aortocaval fistula (ACF) or sham surgery and were examined 24 h and 4 and 12 wk later. Desmin/mitochondrial ultrastructure was examined by transmission electron microscopy (TEM) and immunohistochemistry (IHC). Protein and kinome analysis were performed in isolated cardiomyocytes, and desmin cleavage was assessed by mass spectrometry in left ventricular (LV) tissue. Echocardiography demonstrated a 40% decrease in the LV mass-to-volume ratio with spherical remodeling at 4 wk with ACF and LV systolic dysfunction at 12 wk. Starting at 24 h and continuing to 4 and 12 wk, with ACF there is TEM evidence of extensive mitochondrial clustering, IHC evidence of disorganization associated with desmin breakdown, and desmin protein cleavage verified by Western blot analysis and mass spectrometry. IHC results revealed that ACF cardiomyocytes at 4 and 12 wk had perinuclear translocation of ?B-crystallin from the Z disk with increased ?, ?-unsaturated aldehyde 4-hydroxynonelal. Use of protein markers with verification by TUNEL staining and kinome analysis revealed an absence of cardiomyocyte apoptosis at 4 and 12 wk of ACF. Significant increases in protein indicators of mitophagy were countered by a sixfold increase in p62/sequestosome-1, which is indicative of an inability to complete autophagy. An early and continuous disruption of the desmin/mitochondrial architecture, accompanied by oxidative stress and inhibition of apoptosis and mitophagy, suggests its causal role in LV dilatation and systolic dysfunction in VO.NEW & NOTEWORTHY This study provides new evidence of early onset (24 h) and continuous (4-12 wk) desmin misarrangement and disruption of the normal sarcomeric and mitochondrial architecture throughout the progression of volume overload heart failure, suggesting a causal link between desmin cleavage and mitochondrial disorganization and damage.

Project description:Importance:Cardiac troponin is associated with incident heart failure and greater left ventricular (LV) mass. Its association with LV systolic and diastolic functions is unclear. Objectives:To define the association of high-sensitivity cardiac troponin T (hs-cTnT) with LV systolic and diastolic functions in the general population, and to evaluate the extent to which that association accounts for the correlation between hs-cTnT concentration and incident heart failure overall, heart failure with preserved LV ejection fraction (LVEF; HFpEF), and heart failure with LVEF less than 50%. Design, Setting, and Participants:This analysis of the Atherosclerosis Risk in Communities (ARIC) Study, an ongoing epidemiologic cohort study in US communities, included participants without cardiovascular disease (n = 4111). Available hs-cTnT measurements for participants who attended ARIC Study visits 2 (1990 to 1992), 4 (1996 to 1998), and 5 (2011 to 2013) were assessed cross-sectionally against echocardiographic measurements taken at visit 5 and against incident health failure after visit 5. Changes in hs-cTnT concentrations from visits 2 and 4 were also examined. Data analyses were performed from August 2017 to July 2018. Main Outcomes and Measures:Cardiac structure and function by echocardiography at visit 5, and incident heart failure during a median 4½ years follow-up after visit 5. Results:Of the 6538 eligible participants, 4111 (62.9%) without cardiovascular disease were included. Among these participants, 2586 (62.9%) were female, and the mean (SD) age was 75 (5) years. Median (interquartile range) hs-cTnT concentration at visit 5 was 9 (7-14) ng/L and was detectable in 3946 participants (96.0%). After adjustment for demographic and clinical covariates, higher hs-cTnT levels were associated with greater LV mass index (adjusted mean [SE] for group 1: 33.8 [0.5] vs group 5: 40.1 [0.4]; P?for trend <?.001) and with worse diastolic function, including lower tissue Doppler imaging e' (6.00 [0.07] vs 5.54 [0.06]; P?for trend <?.001), higher E/e' ratio (11.4 [0.2] vs 12.9 [0.1]; P?for trend <?.001), and greater left atrial volume index (23.4 [0.4] vs 26.4 [0.3]; P?for trend <?.001), independent of LV mass index; hs-cTnT level was not associated with measures of LV systolic function. Accounting for diastolic function attenuated the association of hs-cTnT concentration with incident HFpEF by 41% and the association with combined heart failure with midrange and reduced ejection fraction combined (LVEF <50) by 17%. Elevated hs-cTnT concentration and diastolic dysfunction were additive risk factors for incident heart failure. For any value of late-life hs-cTnT levels, longer duration of detectable hs-cTnT from midlife to late life was associated with greater LV mass in late life but not with worse LV systolic or diastolic function. Conclusions and Relevance:This study shows that higher hs-cTnT concentrations were associated with worse diastolic function, irrespective of LV mass, but not with systolic function; these findings suggest that high levels of hs-cTnT may serve as an early marker of subclinical alterations in diastolic function that may lead to a predisposition to heart failure.

Project description:BackgroundAllogeneic hematopoietic stem cell transplantation (allo-HSCT), a potentially curative therapy for malignant and nonmalignant diseases, is being increasingly used in younger patients. Although allo-HSCT survivors have an established increased risk of cardiovascular disease, there is limited knowledge of the long-term effects on cardiac function in survivors.ObjectivesThe purpose of this study was to describe left ventricular (LV) systolic function in long-term allo-HSCT survivors treated in childhood, adolescence, or early adulthood.MethodsOur cross-sectional cohort study included 104 patients (56% women), age 18 ± 10 years at time allo-HSCT with 17 ± 6 years of follow-up. Echocardiography included 2-dimensional (2D) and 3-dimensional (3D) analyses and speckle tracking imaging. In total, 55 healthy control subjects with a similar age, sex, and body mass index were used for comparison. Left ventricular systolic dysfunction (LVSD) was defined as reduced 2D left ventricular ejection fraction (LVEF) of <52% in men and <54% in women, and/or a reduced global longitudinal strain (GLS) of ≥-17%. Multivariable linear regression was used to determine independent predictors of 2D-LVEF and GLS.ResultsAllo-HSCT survivors had significantly reduced LV systolic function compared with control subjects: 2D-LVEF (55.2 ± 5.8% vs. 59.0 ± 2.9%; p < 0.001), 3D LVEF (54.0 ± 5.1% vs. 57.6 ± 2.7%; p < 0.001), and GLS (-17.5 ± 2.2% vs. -19.8 ± 1.4%; p < 0.001). LVSD was found in 44.2%, of whom 28.3% were symptomatic. Clinical factors independently associated with 2D-LVEF and/or GLS included age, anthracyclines, graft versus host disease (GVHD), heart rate, and hypertension. In the 45% of survivors pre-treated with anthracyclines, the effect of anthracyclines on 2D-LVEF and GLS was dose-dependent.ConclusionsLVSD is common in long-term survivors of allo-HSCT treated in their youth. Pre-HSCT therapies with anthracyclines, age, heart rate, hypertension, and graft versus host disease are associated with measures of LV function.

Dataset Information

Long-Term Outcomes of Adults With Heart Failure by Left Ventricular Systolic Function Status.

Publications

Long-Term Outcomes of Adults With Heart Failure by Left Ventricular Systolic Function Status.

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