Elsevier

Heart Failure Clinics

Volume 10, Issue 3, July 2014, Pages 389-398
Heart Failure Clinics

Causes and Pathophysiology of Heart Failure with Preserved Ejection Fraction

https://doi.org/10.1016/j.hfc.2014.04.002Get rights and content

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Key points

  • The pathophysiology of heart failure with preserved ejection fraction (HFPEF) is driven by interactions among age-dependent and gender-dependent characteristics of ventricular-arterial coupling and various predisposing comorbidities and risk factors.

  • Ventricular diastolic dysfunction is central in the pathogenesis of HFPEF caused by an increased ventricular stiffness and is responsible for limited exercise tolerance.

  • At tissue, cellular, and molecular levels, concentric myocardial hypertrophy,

Interaction Between the Heart and Vasculature Is the Achilles Heel of the Cardiovascular System

HFPEF is increasingly recognized as a disease of abnormal ventricular-arterial coupling in association with decreased exercise tolerance.9 To understand the main pathologic pathways leading to this exercise intolerance, basic issues of hemodynamic coupling between the heart and the vasculature should be reviewed under physiologic and pathologic conditions.

The term of ventricular-arterial coupling refers to an interaction between the heart and the vascular system, because the stroke volume (SV)

Risk factors and comorbidities as triggers in HFPEF

Comorbidities have major influence on the pathogenesis of HFPEF. In addition to the primary age-dependent derangements between the myocardium and the vascular system,18 various comorbidities may evoke additional adverse effects on ventricular and vascular functions45 (Fig. 2). Moreover, the prognosis of HFPEF with comorbidities is worse than can be expected with comorbidities alone.46

Because multiple comorbidities influence the prognosis of HFPEF, their targeted treatment takes priority and may

Cellular and molecular mechanisms of increased stiffness: translation of comorbidities to pathophysiology

Myocardial remodeling in HFPEF differs from that in HFREF, in which myocardial remodeling is dominated by cardiomyocyte loss.50 In contrast, in HFPEF, numerous comorbidities result in cellular and molecular changes that promote cardiac and vascular stiffening and contribute to LV diastolic dysfunction (Fig. 3).

Summary

The pathophysiology of HFPEF is driven by interactions among age-dependent and gender-dependent characteristics of ventricular-arterial coupling and various predisposing comorbidities and risk factors. Ventricular diastolic dysfunction is central in the pathogenesis of HFPEF as a result of increased ventricular stiffness and it is responsible for limited exercise tolerance. At tissue, cellular, and molecular levels, concentric myocardial hypertrophy, alterations in ECM and fibrosis,

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    This work was supported by the Social Renewal Operational Programme [TÁMOP-4.2.2.A-11/1/KONV-2012-0045], by a Hungarian Scientific Research Fund [OTKA K 109083], and by the European Union Project FP7-HEALTH-2010: “MEDIA-Metabolic Road to Diastolic Heart Failure” MEDIA-261409.

    The authors have nothing to disclose.

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