Global Differences in Heart Failure With Preserved Ejection Fraction

Tromp, Jasper; Claggett, Brian; Liu, Jiankang; Jackson, Alice; Jhund, Pardeep S.; Køber, Lars; Widimský, Jiří; Boytsov, S. А.; Chopra, Vijay; Anand, Inder; Ge, Junbo; Chen, Chen‐Huan; Maggioni, Aldo P.; Martínez, Felipe A.; Packer, Milton; Pfeffer, Marc A.; Pieske, Burkert; Redfield, Margaret M.; Rouleau, Jean L.; Veldhuisen, Dirk J. van; Zannad, Faı̈ez; Zile, Michael R.; Rizkala, Adel R.; Inubushi-Molessa, Akiko; Lefkowitz, Martin; Shi, Victor; McMurray, John J.V.; Solomon, Scott D.; Lam, Carolyn S.P.

doi:10.1161/circheartfailure.120.007901

Cited by 38 publications

(29 citation statements)

References 25 publications

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“…Figure 2 illustrates regional variations of clinical characteristics and comorbidity burdens based on three major international HFpEF trials: I-Preserve, CHARM-Preserved and PARAGON-HF. [ 72 , 73 ] Patients from North America had a very high prevalence of diabetes and obesity and were at high risk of HF hospitalisation or cardiovascular death. [ 73 ] Patients from Latin America in the I-Preserve and PARAGON-HF trials were more likely to be women than those from other regions and had a relatively high prevalence of hypertension.…”

Section: Racial/ethnic and Geographical Differencesmentioning

confidence: 99%

“…[ 72 , 73 ] Patients from North America had a very high prevalence of diabetes and obesity and were at high risk of HF hospitalisation or cardiovascular death. [ 73 ] Patients from Latin America in the I-Preserve and PARAGON-HF trials were more likely to be women than those from other regions and had a relatively high prevalence of hypertension. Patients from western Europe were often older with a high prevalence of AF and modest risk of HF hospitalisation.…”

Section: Racial/ethnic and Geographical Differencesmentioning

confidence: 99%

“…Demographics and relative prevalence of comorbidities and outcomes (high/low relative to the average of overall patients in trials) across geographical area from three major international clinical trials with HFpEF (I-Preserve,[ 72 ] CHARM-Preserved[ 72 ] and PARAGON-HF[ 73 ]) are presented. Note that regional characteristics of patients from Asia were not available from I-Preserve and CHARM-Preserved, and those from Latin America were not available from CHARM-Preserved.…”

Section: Prognosis Of Hfpefmentioning

confidence: 99%

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Epidemiology and Clinical Features of Heart Failure with Preserved Ejection Fraction

et al. 2022

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Heart failure (HF) with preserved ejection (HFpEF) constitutes a large and growing proportion of patients with HF around the world, and is now responsible for more than half of all HF cases in ageing societies. While classically described as a condition of elderly, hypertensive women, recent studies suggest heterogeneity in clinical phenotypes involving differential characteristics and pathophysiological mechanisms. Despite a paucity of disease-modifying therapy for HFpEF, an understanding of phenotypic similarities and differences among patients with HFpEF around the world provides the foundation to recognise the clinical condition for early treatment, as well as to identify modifiable risk factors for preventive intervention. This review summarises the epidemiology of HFpEF, its common clinical features and risk factors, as well as differences by age, comorbidities, race/ethnicity and geography.

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Section: Racial/ethnic and Geographical Differencesmentioning

confidence: 99%

Section: Racial/ethnic and Geographical Differencesmentioning

confidence: 99%

Section: Prognosis Of Hfpefmentioning

confidence: 99%

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Epidemiology and Clinical Features of Heart Failure with Preserved Ejection Fraction

et al. 2022

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“…Patients with HFpEF are generally older, more often female and have a predominance of comorbidities, such as hypertension, obesity, type 2 diabetes, atrial fibrillation, renal dysfunction, etc. ( 11 , 12 ). However, the specific etiologies by which patients develop HFpEF are variable.…”

Section: Introductionmentioning

confidence: 99%

“…Although HFpEF is greatly impacted by the obesity and diabetes pandemic, hypertension remains the most prevalent and modifiable risk factor in HFpEF and is implicated in both its pathogenesis and prognosis ( 12 , 29 ). Hypertensive HFpEF pathophysiology extends beyond the emphasis on LV hypertrophy development and diastolic dysfunction to impaired myocardial contractility, left atrial myopathy, cardiomyocyte remodeling, macro- and microvascular dysfunction, to systemic inflammation, fibrosis, and collagen deposition.…”

Section: Introductionmentioning

confidence: 99%

Proteomic and phosphoproteomic profiling in heart failure with preserved ejection fraction (HFpEF)

Valero-Muñoz

Saw

Hekman

et al. 2022

Front. Cardiovasc. Med.

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Although the prevalence of heart failure with preserved ejection fraction (HFpEF) is increasing, evidence-based therapies for HFpEF remain limited, likely due to an incomplete understanding of this disease. This study sought to identify the cardiac-specific features of protein and phosphoprotein changes in a murine model of HFpEF using mass spectrometry. HFpEF mice demonstrated moderate hypertension, left ventricle (LV) hypertrophy, lung congestion and diastolic dysfunction. Proteomics analysis of the LV tissue showed that 897 proteins were differentially expressed between HFpEF and Sham mice. We observed abundant changes in sarcomeric proteins, mitochondrial-related proteins, and NAD-dependent protein deacetylase sirtuin-3 (SIRT3). Upregulated pathways by GSEA analysis were related to immune modulation and muscle contraction, while downregulated pathways were predominantly related to mitochondrial metabolism. Western blot analysis validated SIRT3 downregulated cardiac expression in HFpEF vs. Sham (0.8 ± 0.0 vs. 1.0 ± 0.0; P < 0.001). Phosphoproteomics analysis showed that 72 phosphosites were differentially regulated between HFpEF and Sham LV. Aberrant phosphorylation patterns mostly occurred in sarcomere proteins and nuclear-localized proteins associated with contractile dysfunction and cardiac hypertrophy. Seven aberrant phosphosites were observed at the z-disk binding region of titin. Additional agarose gel analysis showed that while total titin cardiac expression remained unaltered, its stiffer N2B isoform was significantly increased in HFpEF vs. Sham (0.144 ± 0.01 vs. 0.127 ± 0.01; P < 0.05). In summary, this study demonstrates marked changes in proteins related to mitochondrial metabolism and the cardiac contractile apparatus in HFpEF. We propose that SIRT3 may play a role in perpetuating these changes and may be a target for drug development in HFpEF.

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Heart failure with preserved ejection fraction phenogroup classification using machine learning

et al. 2023

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Aims Heart failure (HF) with preserved ejection fraction (HFpEF) is a complex syndrome with a poor prognosis. Phenotyping is required to identify subtype-dependent treatment strategies. Phenotypes of Japanese HFpEF patients are not fully elucidated, whose obesity is much less than Western patients. This study aimed to reveal model-based phenomapping using unsupervised machine learning (ML) for HFpEF in Japanese patients. Methods and resultsWe studied 365 patients with HFpEF (left ventricular ejection fraction >50%) as a derivation cohort from the Nara Registry and Analyses for Heart Failure (NARA-HF), which registered patients with hospitalization by acute decompensated HF. We used unsupervised ML with a variational Bayesian-Gaussian mixture model (VBGMM) with common clinical variables. We also performed hierarchical clustering on the derivation cohort. We adopted 230 patients in the Japanese Heart Failure Syndrome with Preserved Ejection Fraction Registry as the validation cohort for VBGMM. The primary endpoint was defined as all-cause death and HF readmission within 5 years. Supervised ML was performed on the composite cohort of derivation and validation. The optimal number of clusters was three because of the probable distribution of VBGMM and the minimum Bayesian information criterion, and we stratified HFpEF into three phenogroups. Phenogroup 1 (n = 125) was older (mean age 78.9 ± 9.1 years) and predominantly male (57.6%), with the worst kidney function (mean estimated glomerular filtration rate 28.5 ± 9.7 mL/min/1.73 m 2 ) and a high incidence of atherosclerotic factor. Phenogroup 2 (n = 200) had older individuals (mean age 78.8 ± 9.7 years), the lowest body mass index (BMI; 22.78 ± 3.94), and the highest incidence of women (57.5%) and atrial fibrillation (56.5%). Phenogroup 3 (n = 40) was the youngest (mean age 63.5 ± 11.2) and predominantly male (63.5 ± 11.2), with the highest BMI (27.46 ± 5.85) and a high incidence of left ventricular hypertrophy. We characterized these three phenogroups as atherosclerosis and chronic kidney disease, atrial fibrillation, and younger and left ventricular hypertrophy groups, respectively. At the primary endpoint, Phenogroup 1 demonstrated the worst prognosis (Phenogroups 1-3: 72.0% vs. 58.5% vs. 45%, P = 0.0036). We also successfully classified a derivation cohort into three similar phenogroups using VBGMM. Hierarchical and supervised clustering successfully showed the reproducibility of the three phenogroups. Conclusions ML could successfully stratify Japanese HFpEF patients into three phenogroups (atherosclerosis and chronic kidney disease, atrial fibrillation, and younger and left ventricular hypertrophy groups).

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Global Differences in Heart Failure With Preserved Ejection Fraction

Cited by 38 publications

References 25 publications

Epidemiology and Clinical Features of Heart Failure with Preserved Ejection Fraction

Epidemiology and Clinical Features of Heart Failure with Preserved Ejection Fraction

Proteomic and phosphoproteomic profiling in heart failure with preserved ejection fraction (HFpEF)

Heart failure with preserved ejection fraction phenogroup classification using machine learning

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