How do patients with heart failure with preserved ejection fraction die?

Chan, Michelle Mei Fung; Lam, Carolyn S.P.

doi:10.1093/eurjhf/hft062

Cited by 187 publications

(167 citation statements)

References 55 publications

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“…Half of these people have normal left ventricular ejection fraction (EF) >50% and are classified as having HF with preserved ejection fraction (HFpEF) 4. While the morbidity and mortality of HF with reduced ejection fraction (HFrEF) is improving,5 outcomes for HFpEF are unchanged 6, 7, 8…”

Section: Introductionmentioning

confidence: 99%

Fibroblast Growth Factor‐23 and Heart Failure With Reduced Versus Preserved Ejection Fraction: MESA

Almahmoud

Soliman

Bertoni

et al. 2018

JAHA

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BackgroundHigher fibroblast growth factor‐23 (FGF‐23) levels are associated with incident heart failure (HF) in MESA (the Multiethnic Study of Atherosclerosis). FGF‐23 is also associated with left ventricular hypertrophy. Whether the FGF‐23 association with HF is similar for heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF) is not well established.Methods and ResultsWe studied 6542 participants (mean age 62±10 years, 53% women, mean estimated glomerular filtration rate of 81±18 mL/min per 73 m2) from MESA who were free of cardiovascular disease at baseline (2000–2002). HF events were ascertained by an adjudication committee for a median follow‐up of 12.1 years. We classified HF events as HFrEF (ejection fraction [EF] <50%) or HFpEF [EF] ≥50%) at the time of diagnosis. Cox proportional hazard regression was used to compute hazard ratios and 95% confidence intervals for the association between baseline serum FGF‐23 and incident HFrEF and HFpEF. A total of 134 events were classified as HFpEF, 151 HFrEF, and 49 unknown EF. Following imputation, 149 were classified as HFpEF, 176 HFrEF, and 291 participants had HF (34 participants had HFpEF then HFrEF). In the fully adjusted model, higher FGF‐23 levels were associated with incident HFpEF but not with HFrEF (hazard ratio 1.29, 95% confidence interval, 1.08–1.54) versus (hazard ratio 1.04, 95% confidence interval, 0.84–1.29) for each 20 pg/mL higher serum FGF‐23 concentration.Conclusions FGF‐23 association with HF is driven by the association with HFpEF but not with HFrEF in a population‐based cohort. Further studies are needed to determine the pathological mechanisms mediating this association.

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Section: Introductionmentioning

confidence: 99%

Fibroblast Growth Factor‐23 and Heart Failure With Reduced Versus Preserved Ejection Fraction: MESA

Almahmoud

Soliman

Bertoni

et al. 2018

JAHA

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“…Over the past 3 decades, while the prevalence of HF with reduced ejection fraction (EF) or systolic HF has remained stable, HFpEF has increased commensurately with the aging of the population at a rate of 1% per year 3. Hospitalizations for HFpEF are increasing relative to HF with reduced ejection fraction,1 and the mortality rates from HFpEF have ranged from 10% to 30% per year in epidemiologic studies 5. The cost associated with this condition is high and poses a significant burden on the healthcare system 6.…”

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confidence: 99%

Prognostic Significance of Baseline Serum Sodium in Heart Failure With Preserved Ejection Fraction

Patel

Kurgansky

Imran

et al. 2018

JAHA

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BackgroundThe purpose of this study was to evaluate the relationship between serum sodium at the time of diagnosis and long term clinical outcomes in a large national cohort of patients with heart failure with preserved ejection fraction.Methods and ResultsWe studied 25 440 patients with heart failure with preserved ejection fraction treated at Veterans Affairs medical centers across the United States between 2002 and 2012. Serum sodium at the time of heart failure diagnosis was analyzed as a continuous variable and in categories as follows: low (115.00–134.99 mmol/L), low‐normal (135.00–137.99 mmol/L), referent group (138.00–140.99 mmol/L), high normal (141.00–143.99 mmol/L), and high (144.00–160.00 mmol/L). Multivariable Cox regression and negative binomial regression were performed to estimate hazard ratios (95% confidence interval [CI]) and incidence density ratios (95% CI) for the associations of serum sodium with mortality and hospitalizations (heart failure and all‐cause), respectively. The average age of patients was 70.8 years, 96.2% were male, and 14% were black. Compared with the referent group, low, low‐normal, and high sodium values were associated with 36% (95% CI, 28%–44%), 6% (95% CI, 1%–12%), and 9% (95% CI, 1%–17%) higher risk of all‐cause mortality, respectively. Low and low‐normal serum sodium were associated with 48% (95% CI, 10%–100%) and 38% (95% CI, 8%–77%) higher risk of number of days of heart failure hospitalizations per year, and with 44% (95% CI, 32%–56%) and 18% (95% CI, 10%–27%) higher risk of number of days of all‐cause hospitalizations per year, respectively.ConclusionsBoth elevated and reduced serum sodium, including values currently considered within normal range, are associated with adverse outcomes in patients with heart failure with preserved ejection fraction.

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“…Cardiac conduction slowing is a major determinant of life‐threatening arrhythmias in patients with heart failure (HF) 1, 2, 3. In failing hearts, reduced sodium current (I Na ) contributes to slowed conduction 4, 5, 6.…”

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Sodium Channel Remodeling in Subcellular Microdomains of Murine Failing Cardiomyocytes

Rivaud

Agullo‐Pascual

Lin

et al. 2017

JAHA

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BackgroundCardiac sodium channel (NaV1.5) dysfunction contributes to arrhythmogenesis during pathophysiological conditions. Nav1.5 localizes to distinct subcellular microdomains within the cardiomyocyte, where it associates with region‐specific proteins, yielding complexes whose function is location specific. We herein investigated sodium channel remodeling within distinct cardiomyocyte microdomains during heart failure.Methods and ResultsMice were subjected to 6 weeks of transverse aortic constriction (TAC; n=32) to induce heart failure. Sham–operated on mice were used as controls (n=20). TAC led to reduced left ventricular ejection fraction, QRS prolongation, increased heart mass, and upregulation of prohypertrophic genes. Whole‐cell sodium current (INa) density was decreased by 30% in TAC versus sham–operated on cardiomyocytes. On macropatch analysis, INa in TAC cardiomyocytes was reduced by 50% at the lateral membrane (LM) and by 40% at the intercalated disc. Electron microscopy and scanning ion conductance microscopy revealed remodeling of the intercalated disc (replacement of [inter‐]plicate regions by large foldings) and LM (less identifiable T tubules and reduced Z‐groove ratios). Using scanning ion conductance microscopy, cell‐attached recordings in LM subdomains revealed decreased INa and increased late openings specifically at the crest of TAC cardiomyocytes, but not in groove/T tubules. Failing cardiomyocytes displayed a denser, but more stable, microtubule network (demonstrated by increased α‐tubulin and Glu‐tubulin expression). Superresolution microscopy showed reduced average NaV1.5 cluster size at the LM of TAC cells, in line with reduced INa.ConclusionsHeart failure induces structural remodeling of the intercalated disc, LM, and microtubule network in cardiomyocytes. These adaptations are accompanied by alterations in NaV1.5 clustering and INa within distinct subcellular microdomains of failing cardiomyocytes.

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How do patients with heart failure with preserved ejection fraction die?

Cited by 187 publications

References 55 publications

Fibroblast Growth Factor‐23 and Heart Failure With Reduced Versus Preserved Ejection Fraction: MESA

Fibroblast Growth Factor‐23 and Heart Failure With Reduced Versus Preserved Ejection Fraction: MESA

Prognostic Significance of Baseline Serum Sodium in Heart Failure With Preserved Ejection Fraction

Sodium Channel Remodeling in Subcellular Microdomains of Murine Failing Cardiomyocytes

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