Regional Adipose Distribution and its Relationship to Exercise Intolerance in Older Obese Patients Who Have Heart Failure With Preserved Ejection Fraction

Haykowsky, Mark J.; Nicklas, Barbara J.; Brubaker, Peter H.; Hundley, W. Gregory; Brinkley, Tina E.; Upadhya, Bharathi; Becton, J. Thomas; Nelson, Michael D.; Chen, Haiying; Kitzman, Dalane W.

doi:10.1016/j.jchf.2018.06.002

Cited by 114 publications

(122 citation statements)

References 45 publications

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“…A recent study enrolled a group of metabolic obese HFpEF patients and measured their total body adiposity (visceral fat and peritoneal fat) and regional adiposity (epicardial fat). These authors concluded that regional adipose deposition might have important adverse consequences and that targeting intra‐abdominal and intermuscular fat could potentially improve exercise intolerance . Interestingly, our previous study found that visceral adipose tissue was associated with the development of LV diastolic dysfunction when adjusted for possible confounding factors in a group of obese patients, but that these effects were possibly caused by low‐grade inflammation .…”

Section: Discussionmentioning

confidence: 96%

“…These authors concluded that regional adipose deposition might have important adverse consequences and that targeting intra-abdominal and intermuscular fat could potentially improve exercise intolerance. 26 Interestingly, our previous study found that visceral adipose tissue was associated with the development of LV diastolic dysfunction when adjusted for possible confounding factors in a group of obese patients, but that these effects were possibly caused by low-grade inflammation. 27 On the other hand, local adipose tissue deposition, such as epicardial fat, can change from a healthy to an unhealthy state when patients move from a healthy condition to obesity or HFpEF.…”

Section: Myocardial Triglycerides and Women With Hfpefmentioning

confidence: 91%

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Myocardial adipose deposition and the development of heart failure with preserved ejection fraction

Lee

Hsu

et al. 2019

European J of Heart Fail

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Aims It has been proposed that an increase of myocardial adiposity is related to left ventricular (LV) diastolic dysfunction. The specific roles of myocardial steatosis including epicardial fat and intramyocardial fat for diastolic function are unknown in those patients suffering heart failure (HF) with reduced (HFrEF) or preserved ejection fraction (HFpEF). This study aims to determine the complex relationship between myocardial adiposity in patients with HFrEF or HFpEF. Methods and results Using cardiac magnetic resonance imaging (CMRI), myocardial steatosis was measured in 305 subjects (34 patients with HFrEF, 163 with HFpEF, and 108 non‐HF controls). We also evaluated cardiac structure and diastolic and systolic function by echocardiography and CMRI. Patients with HFpEF had significantly more intramyocardial fat than HFrEF patients or non‐HF controls [intramyocardial fat content (%), 1.56 (1.26, 1.89) vs. 0.75 (0.50, 0.87) and 1.0 (0.79, 1.15), P < 0.05]. Intramyocardial fat amount (%) was higher in HFpEF women than in men [1.91% (1.17%, 2.32%) vs. 1.22 (0.87%, 2.02%), P = 0.01]. When estimated by CMRI (left ventricular peak filling rate), echocardiographic E/e′ level, or left atrial volume index, intramyocardial fat correlated with LV diastolic dysfunction parameters in HFpEF patients, and this was independent of age, co‐morbidities, body mass index, gender, and myocardial fibrosis (standardized coefficient: β = −0.34, P = 0.03; β = 0.29, P = 0.025; and β = 0.25, P = 0.02, respectively). Conclusions Patients with HFpEF had significantly more intramyocardial fat than HFrEF patients or non‐HF controls. Independent of risk factors or gender, intramyocardial fat correlated with LV diastolic dysfunction parameters in HFpEF patients.

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Section: Discussionmentioning

confidence: 96%

Section: Myocardial Triglycerides and Women With Hfpefmentioning

confidence: 91%

Myocardial adipose deposition and the development of heart failure with preserved ejection fraction

Lee

Hsu

et al. 2019

European J of Heart Fail

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“…143,144 Increased epicardial fat volume is positively correlated with markers of myocardial injury. Identification of specific phenotypes may be helpful.…”

Section: Different Phenotypesmentioning

confidence: 99%

“…These patients have specific characteristics, such as an increase in epicardial fat, total heart volume, and right ventricular filling pressure. 143,144 Increased epicardial fat volume is positively correlated with markers of myocardial injury. 145 Neurohormonal activation with heightened betaadrenergic drive and increased aldosterone and neprilysin activity leading to myocardial fibrosis and diastolic dysfunction are possible specific mechanisms in these patients.…”

Section: Different Phenotypesmentioning

confidence: 99%

Highlights in heart failure

et al. 2019

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Heart failure (HF) remains a major cause of mortality, morbidity, and poor quality of life. It is an area of active research. This article is aimed to give an update on recent advances in all aspects of this syndrome. Major changes occurred in drug treatment of HF with reduced ejection fraction (HFrEF). Sacubitril/valsartan is indicated as a substitute to ACEi/ARBs after PARADIGM-HF (hazard ratio [HR], 0.80; 95% confidence interval [CI], 0.73 to 0.87 for sacubitril/valsartan vs. enalapril for the primary endpoint and Wei, Lin and Weissfeld HR 0.79, 95% CI 0.71-0.89 for recurrent events). Its initiation was then shown as safe and potentially useful in studies in patients hospitalized for acute HF. More recently, DAPA-HF trial showed the beneficial effects of the sodium-glucose transporter type 2 (SGLT2) inhibitor dapaglifozin vs. placebo, added to optimal standard therapy [HR, 0.74; 95% CI, 0.65 to 0.85;0.74; 95% CI, 0.65 to 0.85 for the primary endpoint]. Trials with other SGLT 2 inhibitors and in other patients, such as those with HF with preserved ejection fraction (HFpEF) or with recent decompensation, are ongoing. Multiple studies showed the unfavourable prognostic significance of abnormalities in serum potassium levels. Potassium lowering agents may allow initiation and titration of mineralocorticoid antagonists in a larger proportion of patients. Meta-analyses suggest better outcomes with ferric carboxymaltose in patients with iron deficiency. Drugs effective in HFrEF may be useful also in HF with mid-range ejection fraction. Better diagnosis and phenotype characterization seem warranted in HF with preserved ejection fraction. These and other burning aspects of HFpEF research are summarized and reviewed in this article.A multiparametric approach is often proposed for risk stratification of HF patients. The prognostic accuracy of the metabolic exercise test data combined with cardiac and kidney indexes risk score was found as superior to the HF Survival Score and Seattle HF model risk scores in a cohort of 6112 1106 D. Tomasoni et al.

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“…One of the likely reasons for the lack of effective therapies for HFpEF is that no currently used HF therapies directly target the fundamental metabolic derangements that lead to HFpEF phenotype—namely, obesity and insulin resistance. A plethora of evidence now indicate that excess adipose tissue likely plays the over‐arching, pivotal role in the development, progression and adverse outcomes in HFpEF …”

Section: Effects Of Sodium‐glucose Cotransports‐2 Inhibitors (Sglt‐2imentioning

confidence: 99%

Effects of sodium glucose cotransporter type 2 inhibitors on heart failure

Nassif

Kosiborod

2019

Diabetes Obesity Metabolism

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patients with type 2 diabetes have a 2-5-fold increase risk of incident HF. 4,5 The association between metabolic derangements is an even stronger predictor of HFpEF than HFrEF. Both obesity (and even more specifically, central adiposity) and insulin resistance are major predictors of incident HFpEF, but not HFrEF. 6 Moreover, patients with T2DM who develop concomitant HF experience high morbidity and mortality, with estimates among Medicare patients placing 5-year survival near 25%. 4 Recent data from National Diabetes Register in Sweden suggest when all traditional risk factors for ASCVD are well controlled, patients with T2D have an equivalent associated risk of ASCVD events when compared to those without T2D. However, they continue to have a substantially greater risk of developing HFindicating that traditional risk factor control is insufficient from a HF prevention standpoint, and highlighting the need for novel, more effective strategies for both prevention and treatment of HF in patients with T2D. 7 A growing body of literature is now supporting the concept that HFpEF is primarily a consequence of obesity and systemic metabolic derrangements. 8-14 It is therefore perhaps not surprising that nearly all evidence based treatment for HFrEF (beta blockers, ACE-inhibitors, digoxin, nitrates, etc.) have failed to improve outcomes in HFpEF. One of the likely reasons for the lack of effective therapies for HFpEF is that no currently used HF therapies directly target the fundamental metabolic derangements that lead to HFpEF phenotype-namely, obesity and insulin resistance. A plethora of evidence now indicate that excess adipose tissue likely plays the over-arching, pivotal role in the development, progression and adverse outcomes in HFpEF. 15,16 After 2008, following the regulatory guidance change for assessment of novel glucose-lowering agents, 17 both the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) world benefits were found in the US Department of Defense Military Health System analysis. 43 After propensity matching, 25 258 patients were followed for a median of 1.6 years, and initiation of SGLT-2i vs comparator agents was associated with a significantly lower risk of allcause mortality or HFF (1.73 vs 3.01 events per 100 person-years; HR, 0.57 [95% CI, 0.50-0.65]). 43The mechanism(s) of action for the HF benefits of SGLT-2i remain a subject of debate. Given that the estimates for HF hospitalization begin to separate within weeks and are maintained for several years, it is highly likely that mechanisms beyond glucose lowering are behind the reduction in HF events. 32,34,44 It is also likely that there is no singular mechanism that explains all of the HF benefits. However, some of the leading theories refer to naturiesis and volume reduction, improved oxygen supply via an increase in hematocrit, a metabolic shift towards the consumption of more ketone bodies, a reduction of glomerular pressure and reduced oxygen consumption in the proximal tubule of the kidneys, altered Na+/H+ exc...

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Regional Adipose Distribution and its Relationship to Exercise Intolerance in Older Obese Patients Who Have Heart Failure With Preserved Ejection Fraction

Cited by 114 publications

References 45 publications

Myocardial adipose deposition and the development of heart failure with preserved ejection fraction

Myocardial adipose deposition and the development of heart failure with preserved ejection fraction

Highlights in heart failure

Effects of sodium glucose cotransporter type 2 inhibitors on heart failure

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