Heart failure with preserved ejection fraction: Refocusing on diastole

Abbate, Antonio; Arena, Ross; Abouzaki, Nayef; Tassell, Benjamín W. Van; Canada, Justin M.; Shah, Keyur B.; Biondi‐Zoccai, Giuseppe; Voelkel, Norbert F.

doi:10.1016/j.ijcard.2014.11.106

Cited by 91 publications

(99 citation statements)

References 107 publications

(161 reference statements)

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“…Nevertheless, these findings may have diagnostic, prognostic, and therapeutic implications. From a diagnostic standpoint, the association of the diastolic parameters and in particular of the E′ velocity with impaired functional capacity reinforces the view that impaired diastolic function is key phenomenon in this HFpEF subgroup 1, 11. The close association between E′ velocity with exercise, and of E′ DT , with peak VO 2 , a well‐validated prognostic indicator in HF,6 supports the concept that the severity of the impaired myocardial relaxation is an important factor in the pathophysiology of HFpEF.…”

Section: Discussionsupporting

confidence: 66%

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Impaired myocardial relaxation with exercise determines peak aerobic exercise capacity in heart failure with preserved ejection fraction

et al. 2017

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BackgroundHeart failure with preserved ejection fraction (HFpEF) is a clinical syndrome characterized by impaired exercise capacity due to shortness of breath and/or fatigue. Assessment of diastolic dysfunction at rest and with exercise may provide insight into the pathophysiology of exercise intolerance in HFpEF.AimsTo measure echocardio‐Doppler‐derived parameters of diastolic function as they relate to various indices of aerobic exercise capacity in HFpEF.MethodsWe selected 16 subjects with clinically stable HFpEF, no evidence of volume overload, but impaired functional capacity by cardiopulmonary exercise testing [peak oxygen consumption (VO2)]. We measured the transmitral E and A flow velocities, E/A ratio, and E deceleration time (DT) and tissue Doppler E′ velocity. We also indexed the E′ to the DT, as additional measure of impaired relaxation (E′DT), and calculated the diastolic functional reserve index (DFRI), as the product of E′ at rest and change in E′ with exercise.ResultsE′ velocity, at rest and peak exercise, as well as the DFRI positively correlated with peak VO2, whereas DT, E′DT, and E/E′ with exercise inversely correlated with peak VO2. Of note, the E′DT at rest also significantly predicted E′ velocity at peak exercise (R = +0.81, P < 0.001). Exercise E′ was the only independent predictor of peak VO2 at multivariable analysis (R = +0.67, P = 0.005).ConclusionsThe E′ velocity at peak exercise is a strong and independent predictor of aerobic exercise capacity as measured by peak VO2 in patients with HFpEF, providing the link between abnormal myocardial relaxation with exercise and impaired aerobic exercise capacity in HFpEF.

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Section: Discussionsupporting

confidence: 66%

“…Impaired diastolic reserve, measured as an inadequate increase in myocardial relaxation, is considered a hallmark of HFpEF and is associated with a progressive decline in exercise capacity 1, 5, 8. However, measuring diastolic parameters only at rest may not reveal the severity of limitation in patients suffering from this syndrome.…”

Section: Discussionmentioning

confidence: 99%

Impaired myocardial relaxation with exercise determines peak aerobic exercise capacity in heart failure with preserved ejection fraction

et al. 2017

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“…HEART FAILURE (HF) WITH PRESERVED ejection fraction (HFpEF) is a clinical syndrome of symptoms of HF, such as breathlessness and exercise intolerance, associated with impaired left ventricular (LV) diastolic function in the presence of a normal LV ejection fraction (LVEF Ͼ 50%) (2). HFpEF carries significant morbidity and mortality burdens, and the prevalence of the disease has increased over the past 30 yr (2,17).…”

Section: Chronic Infusion Of Low-dose Angiotensin II In the Mouse Indmentioning

confidence: 99%

“…HFpEF carries significant morbidity and mortality burdens, and the prevalence of the disease has increased over the past 30 yr (2,17). To date, the mechanisms underlying diastolic dysfunction and the progression of HFpEF are poorly understood.…”

Section: Chronic Infusion Of Low-dose Angiotensin II In the Mouse Indmentioning

confidence: 99%

A mouse model of heart failure with preserved ejection fraction due to chronic infusion of a low subpressor dose of angiotensin II

Regan

Mauro

Carbone

et al. 2015

American Journal of Physiology-Heart and Circulatory Physiology

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A, Toldo S. A mouse model of heart failure with preserved ejection fraction due to chronic infusion of a low subpressor dose of angiotensin II. Am J Physiol Heart Circ Physiol 309: H771-H778, 2015. First published July 17, 2015; doi:10.1152/ajpheart.00282.2015.-Heart failure (HF) with preserved ejection fraction (HFpEF) is a clinical syndrome of HF symptoms associated with impaired diastolic function. Although it represents ϳ50% of patients with HF, the mechanisms of disease are poorly understood, and therapies are generally ineffective in reducing HF progression. Animal models of HFpEF not due to pressure or volume overload are lacking, therefore limiting in-depth understanding of the pathophysiological mechanisms and the development of novel therapies. We hypothesize that a continuous infusion of low-dose angiotensin II (AT II) is sufficient to induce left ventricular (LV) diastolic dysfunction and HFpEF, without increasing blood pressure or inducing LV hypertrophy or dilatation. Osmotic pumps were implanted subcutaneously in 8-wk-old male mice assigned to the AT II (0.2 mg·kg Ϫ1 ·day Ϫ1 ) or volume-matched vehicle (N ϭ 8/group) for 4 wk. We measured systolic and diastolic arterial blood pressures through a tail-cuff transducer, LV dimensions and ejection fraction through echocardiography, and LV relaxation through pulsed-wave Doppler and LV catheterization. Myocardial fibrosis and cardiomyocyte cross-sectional area were measured. AT II infusion had no effects on systemic arterial blood pressure. ATII induced significant impairment in LV diastolic function, as measured by an increase (worsening) in LV isovolumetric relaxation time, myocardial performance index, isovolumetric relaxation time constant, and LV end-diastolic pressure without altering LV dimensions, mass, or ejection fraction. Chronic infusion of low-dose AT II recapitulates the HFpEF phenotype in the mouse, without increasing systemic arterial blood pressure. This mouse model may provide insight into the mechanisms of HFpEF.heart failure with preserved ejection fraction; diastolic dysfunction; animal model; angiotensin II; end-diastolic pressure; isovolumetric relaxation time NEW & NOTEWORTHY Chronic infusion of low-dose angiotensin II in the mouse induces diastolic dysfunction and HFpEF in the absence of pressure overload, LV systolic dysfunction, LV dilatation or hypertrophy, and metabolic abnormalities. This model may be considered a novel tool for mechanistic preclinical studies in HFpEF with translational potential.HEART FAILURE (HF) WITH PRESERVED ejection fraction (HFpEF) is a clinical syndrome of symptoms of HF, such as breathlessness and exercise intolerance, associated with impaired left ventricular (LV) diastolic function in the presence of a normal LV ejection fraction (LVEF Ͼ 50%) (2). HFpEF carries significant morbidity and mortality burdens, and the prevalence of the disease has increased over the past 30 yr (2, 17). To date, the mechanisms underlying diastolic dysfunction and the progression of HFpEF are poorly understood. The path...

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“…While elevated levels help to confirm the diagnosis and generally predict a worse outcome, the absence of elevation does not rule out the diagnosis of HFpEF. 5,6 A common hemodynamic finding in HFpEF is an exaggerated increase in pulmonary capillary wedge pressure and pulmonary artery pressure during exercise with an attenuated increase in cardiac output. 7 An electrocardiogram may indicate LV hypertrophy or atrial enlargement.…”

Section: Clinical Presentationmentioning

confidence: 99%

Treating Heart Failure with Preserved Ejection Fraction: A Challenge for Clinicians

Howard

2015

Hosp Pharm

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Despite a decline in many forms of cardiovascular disease, heart failure (HF) continues to increase. Heart failure with preserved ejection fraction (HFpEF) is common, especially among persons with multiple comorbidities. HFpEF presents many challenges for clinicians due to the incomplete understanding of the underlying mechanisms and lack of consensus on the most effective strategies for treatment. Angiotensin and beta receptor-blocking drugs, which form the cornerstone for the treatment of systolic HF, have failed to show similar benefits in patients with impaired diastolic function. This article provides an overview of drug therapy for HFpEF, including newer agents now under investigation.

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Heart failure with preserved ejection fraction: Refocusing on diastole

Cited by 91 publications

References 107 publications

Impaired myocardial relaxation with exercise determines peak aerobic exercise capacity in heart failure with preserved ejection fraction

Impaired myocardial relaxation with exercise determines peak aerobic exercise capacity in heart failure with preserved ejection fraction

A mouse model of heart failure with preserved ejection fraction due to chronic infusion of a low subpressor dose of angiotensin II

Treating Heart Failure with Preserved Ejection Fraction: A Challenge for Clinicians

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