Effects of Treatment on Exercise Tolerance, Cardiac Function, and Mortality in Heart Failure With Preserved Ejection Fraction

Holland, David J.; Kumbhani, Dharam J.; Ahmed, Salim; Marwick, Thomas H.

doi:10.1016/j.jacc.2010.10.057

Cited by 130 publications

(102 citation statements)

References 56 publications

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“…Ang 1-7 treatment represents a potential new therapeutic tool for the treatment of diabetic cardiomyopathy and HFPEF, in which there is currently limited therapy. 6,50 Although targeting the Ang II type 1 receptor pathway failed to improve the outcome of patients with HFPEF, 6,50 targeting the other aspect of the renin-angiotensin system/ACE2 pathway such as enhancing Ang 1-7 action may represent a novel therapy for HFPEF. (Ang 1-7) in the heart and adipose tissue in the db/db model.…”

Section: Discussionmentioning

confidence: 99%

Angiotensin 1–7 Ameliorates Diabetic Cardiomyopathy and Diastolic Dysfunction in db/db Mice by Reducing Lipotoxicity and Inflammation

Mori

Patel

Alrob

et al. 2014

Circ: Heart Failure

162

126

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Background-The angiotensin-converting enzyme 2 and angiotensin-(1-7) (Ang 1-7)/MasR (Mas receptor) axis are emerging as a key pathway that can modulate the development of diabetic cardiomyopathy. We studied the effects of Ang 1-7 on diabetic cardiomyopathy in db/db diabetic mice to elucidate the therapeutic effects and mechanism of action. Methods and Results-Ang 1-7 was administered to 5-month-old male db/db mice for 28 days via implanted microosmotic pumps. Ang 1-7 treatment ameliorated myocardial hypertrophy and fibrosis with normalization of diastolic dysfunction assessed by pressure-volume loop analysis and echocardiography. The functional improvement by Ang 1-7 was accompanied by a reduction in myocardial lipid accumulation and systemic fat mass and inflammation and increased insulin-stimulated myocardial glucose oxidation. Increased myocardial protein kinase C levels and loss of phosphorylation of extracellular signal-regulated kinase 1/2 were prevented by Ang 1-7. Furthermore, Ang 1-7 treatment decreased cardiac triacylglycerol and ceramide levels in db/db mice, concomitantly with an increase in myocardial adipose triglyceride lipase expression. Changes in adipose triglyceride lipase expression correlated with increased SIRT1 (silent mating type information regulation 2 homolog 1) levels and deacetylation of FOXO1 (forkhead box O1). Conclusions-We identified a novel beneficial effect of Ang 1-7 on diabetic cardiomyopathy that involved a reduction in cardiac hypertrophy and lipotoxicity, adipose inflammation, and an upregulation of adipose triglyceride lipase. Ang 1-7 completely rescued the diastolic dysfunction in the db/db model. Ang 1-7 represents a promising therapy for diabetic cardiomyopathy associated with type 2 diabetes mellitus. (Circ Heart Fail. 2014;7:327-339.)

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Section: Discussionmentioning

confidence: 99%

Angiotensin 1–7 Ameliorates Diabetic Cardiomyopathy and Diastolic Dysfunction in db/db Mice by Reducing Lipotoxicity and Inflammation

Mori

Patel

Alrob

et al. 2014

Circ: Heart Failure

162

126

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“…1] [4]. Therapies of proven benefit in HFrEF have repeatedly been shown to add little if any benefit in HFpEF [5,6]. With the current increases in global life expectancy and significant advances in diagnosis, treatment and secondary prevention of almost all cardiovascular diseases, it is expected that the prevalence of heart failure will continue to rise reaching epidemic levels in both developed and developing countries [7][8][9].…”

Section: Introductionmentioning

confidence: 99%

Heart Failure with Preserved Ejection Fraction

Čulić

2017

N Engl J Med

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Heart failure with preserved ejection fraction (HFpEF) has recently emerged as a major cause of cardiovascular morbidity and mortality. Contrary to initial beliefs, HFpEF is now known to be as common as heart failure with reduced ejection fraction (HFrEF) and carries an unacceptably high mortality rate. With a prevalence that has been steadily rising over the past two decades, it is very likely that HFpEF will represent the dominant heart failure phenotype over the coming few years. The scarcity of trials in this semi-discrete form of heart failure and lack of unified enrolment criteria in the studies conducted to date might have contributed to the current absence of specific therapies. Understanding the epidemiological, pathophysiological and molecular differences (and similarities) between these two forms of heart failure is cornerstone to the development of targeted therapies. Carefully designed studies that adhere to unified diagnostic criteria with the recruitment of appropriate controls and adoption of practical end-points are urgently needed to help identify effective treatment strategies.

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“…Although substantial progress has been made in the management and outcomes of heart failure with reduced ejection fraction (HFREF), outcomes associated with HFPEF remain unchanged 1, 2. Well‐established pharmacological therapies for HFREF have failed to improve prognosis in HFPEF 3, 4, 5, 6. This has largely been attributed to the phenotypic variability and the complex pathophysiological mechanisms underlying the development of HFPEF 7…”

mentioning

confidence: 99%

Effect of Mineralocorticoid Receptor Antagonists on Cardiac Structure and Function in Patients With Diastolic Dysfunction and Heart Failure With Preserved Ejection Fraction: A Meta‐Analysis and Systematic Review

Pandey

Garg

Matulevicius

et al. 2015

JAHA

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BackgroundThere has been an increasing interest in use of mineralocorticoid receptor antagonists (MRAs) in patients with heart failure with preserved ejection fraction (HFPEF). However, a comprehensive evaluation of MRA effects on left ventricular (LV) structure and function in these patients is lacking. In this meta‐analysis, we evaluated the effects of MRAs on LV structure and function among patients with diastolic dysfunction or HFPEF.Methods & ResultsRandomized, controlled clinical trials evaluating the efficacy of MRAs in patients with diastolic dysfunction or HFPEF were included. The primary outcome was change in E/e’, a specific measure of diastolic function. Secondary outcomes included changes in other measures of diastolic function, LV structure, surrogate markers for myocardial fibrosis (carboxy‐terminal peptide of procollagen type I [PICP] and amino‐terminal peptide of pro‐collagen type‐II [PIIINP]), blood pressure, and exercise tolerance. In the pooled analysis, MRA use was associated with significant reduction in E/e’ (weighted mean difference [WMD] [95% confidence interval {CI}]: −1.68 [−2.03 to −1.33]; P<0.0001) and deceleration time (WMD [95% CI]: −12.0 ms [−23.3 to −0.7]; P=0.04) as compared with control, suggesting and improvement in diastolic function. Furthermore, blood pressure and levels of PIIINP and PICP were also significantly reduced with MRA therapy with no significant change in LV mass or dimensions.Conclusion MRA therapy in patients with asymptomatic diastolic dysfunction or HFPEF is associated with significant improvement in diastolic function and markers of cardiac fibrosis without a significant change in LV mass or dimensions.

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Effects of Treatment on Exercise Tolerance, Cardiac Function, and Mortality in Heart Failure With Preserved Ejection Fraction

Abstract: Pharmacotherapy of heart failure with preserved ejection fraction demonstrates a quantifiable improvement in exercise tolerance but not mortality.

Cited by 130 publications

References 56 publications

Angiotensin 1–7 Ameliorates Diabetic Cardiomyopathy and Diastolic Dysfunction in db/db Mice by Reducing Lipotoxicity and Inflammation

Angiotensin 1–7 Ameliorates Diabetic Cardiomyopathy and Diastolic Dysfunction in db/db Mice by Reducing Lipotoxicity and Inflammation

Heart Failure with Preserved Ejection Fraction

Effect of Mineralocorticoid Receptor Antagonists on Cardiac Structure and Function in Patients With Diastolic Dysfunction and Heart Failure With Preserved Ejection Fraction: A Meta‐Analysis and Systematic Review

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