Biological Phenotypes of Heart Failure With Preserved Ejection Fraction

Lewis, Gavin; Schelbert, Erik B.; Williams, Simon G.; Cunnington, Colin; Ahmed, Fozia; McDonagh, Theresa A.; Miller, Chris

doi:10.1016/j.jacc.2017.09.006

Cited by 176 publications

(136 citation statements)

References 117 publications

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“…In particular, patients with HFpEF are a highly heterogeneous group with multiple pathophysiologic factors, and the phenotypic diversity of HFpEF is acknowledged. [42][43][44] In the present study, the results in very old patients with HFpEF are consistent with those of the former studies, whereas the results in younger-old (aged 65-84 y) patients with HFpEF agree with the latter reports. The relationship between COPD and HFpEF is complicated by multiple pathophysiologic mechanisms including both local and systemic factors, and it appears that some such mechanisms differ by age.…”

Section: Discussionsupporting

confidence: 93%

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Younger‐ vs Older‐Old Patients with Heart Failure with Preserved Ejection Fraction

Matsushita

Harada

Miyazaki

et al. 2019

J American Geriatrics Society

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OBJECTIVES Heart failure with preserved ejection fraction (HFpEF) is now recognized as a geriatric syndrome with multifactorial pathophysiology and clinical heterogeneity rather than a solely left ventricular diastolic dysfunction. Because the pathophysiology of HFpEF is suggested to differ by age, this study compared the clinical characteristics and prognostic factors between HFpEF patients aged 65 to 84 years and those aged 85 years or older. DESIGN Retrospective cohort study. SETTING The Tokyo CCU Network including 73 hospitals in Tokyo, Japan. PARTICIPANTS Individuals aged 65 years or older with HFpEF (N = 4305). MEASUREMENTS Very old patients were defined as those aged 85 years or older. Potential risk factors for in‐hospital mortality were selected by univariate analyses, and those with a P value <.10 were used in multivariate Cox regression analysis with forward selection (likelihood ratio) to identify significant factors. RESULTS Prevalence of hypertension was significantly higher in very old patients, whereas prevalence of coronary artery disease, diabetes mellitus, hyperlipidemia, and smoking was significantly higher in patients aged 65 to 84 years. In very old patients, low systolic blood pressure (hazard ratio [HR] = .988), high serum creatinine level (HR = 1.34), and coexisting chronic obstructive pulmonary disease (COPD; HR = 2.01) were identified as independent risk factors for in‐hospital mortality. In contrast, low systolic blood pressure (HR = .987) and low body mass index (HR = .935) were identified as independent risk factors in patients aged 65 to 84 years. CONCLUSION Significant differences were observed in the clinical characteristics and prognostic factors for in‐hospital mortality between HFpEF patients aged 65 to 84 and those 85 years and older. Of note, coexisting COPD was associated with significantly lower survival rate only in patients aged 85 years and older, suggesting the prognostic impact of concomitant pulmonary disease in HFpEF may increase with age. These results have implications for future research and management of older HFpEF patients. J Am Geriatr Soc 00:1–6, 2019. J Am Geriatr Soc 67:2123–2128, 2019

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Section: Discussionsupporting

confidence: 93%

“…These discrepancies might be related to the different clinical situations in these studies, and careful interpretation of each study is required. In particular, patients with HFpEF are a highly heterogeneous group with multiple pathophysiologic factors, and the phenotypic diversity of HFpEF is acknowledged …”

Section: Discussionmentioning

confidence: 99%

Younger‐ vs Older‐Old Patients with Heart Failure with Preserved Ejection Fraction

Matsushita

Harada

Miyazaki

et al. 2019

J American Geriatrics Society

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“…Diastolic dysfunction has a multifactorial aetiology that includes deficiencies or abnormalities in myocardial fibrosis, extracellular matrix, myocardial calcium reuptake, mitochondrial function, myocardial hypertrophy, arterial‐ventricular coupling, and external constraint of excess epicardial fat . Considering the multiple putative mechanisms, it is not surprising that HFpEF has been considered to comprise different phenotypes reflecting the different pathways leading to diastolic dysfunction.…”

Section: Introductionmentioning

confidence: 99%

Hypoxia‐inducible factor 1‐alpha (HIF‐1α) as a factor mediating the relationship between obesity and heart failure with preserved ejection fraction

Warbrick

Rabkin

2019

Obesity Reviews

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Summary Heart failure with preserved ejection fraction (HFpEF), a common condition with an increased mortality, is strongly associated with obesity and the metabolic syndrome. The latter two conditions are associated with increased epicardial fat that can extend into the heart. This review advances the proposition that hypoxia‐inhibitory factor‐1α (HIF‐1α) maybe a key factor producing HFpEF. HIF‐1α, a highly conserved transcription factor that plays a key role in tissue response to hypoxia, is increased in adipose tissue in obesity. Increased HIF‐1α expression leads to expression of a potent profibrotic transcriptional programme involving collagen I, III, IV, TIMP, and lysyl oxidase. The net effect is the formation of collagen fibres leading to fibrosis. HIF‐1α is also responsible for recruiting M1 macrophages that mediate obesity‐associated inflammation, releasing IL‐6, MCP‐1, TNF‐α, and IL‐1β with increased expression of thrombospondin, pro α2 (I) collagen, transforming growth factor β, NADPH oxidase, and connective tissue growth factor. These factors can accelerate cardiac fibrosis and impair cardiac diastolic function. Inhibition of HIF‐1α expression in adipose tissue of mice fed a high‐fat diet suppressed fibrosis and reduces inflammation in adipose tissue. Delineation of the role played by HIF‐1α in obesity‐associated HFpEF may lead to new potential therapies.

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“…The greater requirement for NIV in HFPEF may reflect the burden of obesity and pulmonary vascular disease, skeletal muscle dysfunction, and pulmonary diseases including COPD . For example, up to one‐third of HFPEF patients had COPD and half were obese in one study .…”

Section: Discussionmentioning

confidence: 99%

Respiratory support in acute heart failure with preserved vs reduced ejection fraction

Metkus

Stephens

Schulman

et al. 2019

Clinical Cardiology

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Background There is little evidence addressing the use and differential impact of respiratory support in acute heart failure (AHF) patients with preserved (HFPEF) vs reduced (HFREF) ejection fraction. Therefore, our objective was to determine the usage and clinical outcomes of critical care respiratory support in AHF across the two populations. Hypothesis Respiratory support would be associated with adverse outcome in both HFPEF and HFREF. Methods We identified HFPEF, HFREF, invasive mechanical ventilation (IMV), and noninvasive ventilation (NIV) using International Classification of Disease‐Ninth Edition codes in the National Inpatient Sample between January 1, 2008 and December 31, 2014. We determined rates of IMV and NIV use. We identified predictors of need for IMV and NIV and the association between ventilation strategies and in‐hospital mortality in HFPEF vs HFREF. Results 1.3 million AHF‐HFPEF and 1.7 million AHF‐HFREF hospitalizations were included; 5.98% of AHF HFPEF hospitalizations included NIV and 0.57% included IMV. Among HFREF hospitalizations, fewer (4.1%) included NIV and more (0.93%) included IMV. In HFPEF hospitalization, NIV use was associated with 2.24‐fold increased risk for death compared to no respiratory support in an adjusted model (HR 2.24 95% CI 2.05‐2.44) and IMV use was associated with 2.85‐fold increased risk for death (HR 2.85 95% CI 2.30‐3.53). This increased risk of in‐hospital mortality was similar among HFREF patients. Conclusions Use of respiratory support is increasing among patients with both HFPEF and HFREF and associated with substantially increased mortality in both heart failure subtypes.

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Biological Phenotypes of Heart Failure With Preserved Ejection Fraction

Cited by 176 publications

References 117 publications

Younger‐ vs Older‐Old Patients with Heart Failure with Preserved Ejection Fraction

Younger‐ vs Older‐Old Patients with Heart Failure with Preserved Ejection Fraction

Hypoxia‐inducible factor 1‐alpha (HIF‐1α) as a factor mediating the relationship between obesity and heart failure with preserved ejection fraction

Respiratory support in acute heart failure with preserved vs reduced ejection fraction

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