Heart failure with preserved ejection fraction

Abstract

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.

Keywords: diastolic heart failure; heart failure; heart failure with preserved ejection fraction.

Figure 1.. Secular trends in the prevalence of HFpEF. Data collected from the Mayo Clinic for 4596 patients discharged with a diagnosis of heart failure over a 15-year period (1987–2001). Panel A shows a steady increase in the percentage of patients with heart failure who had preserved ejection fraction (>50%) over the study period. Panel B shows the number of admissions for heart failure in patients with preserved ejection fraction (solid red line) and with reduced ejection fraction (solid black line). The dashed lines represent the 95% confidence intervals. From Theophilus E, et al. with permission.

Figure 2.. Excitation–contraction and inactivation–relaxation coupling in cardiomyocytes. Cardiomyocyte depolarization promotes Ca²⁺ entry through the sarcolemmal L-type Ca²⁺ channels (L–Ca²⁺), leading to Ca²⁺ release for the sarcoplasmic reticulum (SR) through ryanodine receptors (RyR), thereby inducing contraction. During relaxation the four pathways involved in calcium removal from the cytosol are phospholamban (PLB)-modulated uptake of Ca²⁺ into the sarcoplasmic reticulum by a Ca²⁺-ATPase (SERCA), Ca²⁺ extrusion via the sodium-calcium exchanger (NCX), mitochondrial Ca²⁺ uniport and sarcolemmal Ca²⁺-ATPase, with the latter two being responsible for only about 1% of the total. From Roncon-Albuquerque R Jr et al. with permission.

Figure 3.. Left ventricular pressure-volume loop in ventricles with delayed relaxation. Only the bottom half of the pressure-volume loop is shown. The rate of LV pressure decline is much slower in patients with a delayed relaxation pattern of diastolic filling (dashed line) compared to normal subjects (solid line). Left ventricular end-diastolic pressure (LVEDP) remains normal or slightly elevated.

Figure 4.. Left ventricular pressure-volume loop in ventricles with increased stiffness. Only the bottom half of the pressure-volume loop is shown. The slope of the late diastolic pressure volume relation in patients with stiff ventricles (dashed line) is increased leading to an exaggerated response in intraventricular pressure (ΔP) to any given change in volume compared to normal subjects (solid line). Consequently, left ventricular end-diastolic pressure (LVEDP) is markedly elevated.

Figure 5.. HFpEF Diagnostic Algorithm. LVEDVI, left ventricular end-diastolic volume index; mPCW, mean pulmonary capillary wedge pressure; LVEDP, left ventricular end-diastolic pressure; t, time constant of left ventricular relaxation; b, constant of left ventricular chamber stiffness; TD, tissue Doppler; E, early mitral valve flow velocity; E0, early TD lengthening velocity; NT-proBNP, N-terminal-pro brain natriuretic peptide; BNP, brain natriuretic peptide; E/A, ratio of early (E) to late (A) mitral valve flow velocity; DT, deceleration time; LVMI, left ventricular mass index; LAVI, left atrial volume index; Ard, duration of reverse pulmonary vein atrial systole flow; Ad, duration of mitral valve atrial wave flow. From Paulus et al. with permission from Oxford press.