Functional and Metabolic Imaging in Heart Failure with Preserved Ejection Fraction: Promises, Challenges, and Clinical Utility

Fig. 1. Multivariable logistic regression derived odds ratios (OR) for risk factors in developing HFpEF and HFrEF in the 1.8 million US Veterans Affairs population (comprising \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$n=66\,831$$\end{document}n=66831 HFpEF and \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$n=92\,233$$\end{document}n=92233 HFrEF patients). Data are reproduced (with permission) from Gaziano et al. [6], and have been corrected for age, sex, race, and ethnicity. A thin blue line highlights the differences between HFpEF and HFrEF. Abbreviations: ACE, angiotensin converting enzyme; ARB, angiotensin receptor blocker; BMI, body mass index (coefficient per \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs}…

Fig. 2. A Taken together, these factors are sufficient to delineate HFpEF as a very distinct disease from HFrEF. As detailed by Guazzi et al. [28], in HFpEF, concentric myocyte remodelling with increased left ventricular (LV) diastolic stiffness, atrial functional MR, and a stiff left atrium (LA) are the major driving forces to alveolar-capillary stress failure and vascular remodelling, with corresponding differential changes in the end-systolic/end-diastolic pressure-volume relation (ESPVR/EDPVR) compared to healthy controls (shown in blue). B It is worth further stressing that, although not typically caused by an ischaemic origin, HFpEF has a similar mortality to HFrEF following MI, as illustrated here in an “all-comers” Ethiopian cohort HF study reporting outcomes on all HF patients treated at the University of Gondar Referral Hospital between 2010 and 2015 [29]

Fig. 3. A very brief schematic overview of the currently understood pathogenesis of HFpEF. It is important to remember that the HFpEF syndrome is a biventricular process and that the contributions of the right heart are equally important. (1) Increased left ventricular stiffness, and a decreased functional reserve, results in (2) increased left-sided filling pressures with left atrial dilatation and increased left atrial pressure. This leads to increased pulmonary transcapillary hydrostatic pressure, which drives fluid transudation, potentially increasing capillary diameter from the Young-Laplace relation, and resulting in pulmonary congestion (3). Similar maladaptive right heart processes may also occur in parallel. (4) Reduced right ventricular contractile reserve, and reduced coupling of the right ventricle to the pulmonary circulation or RV-PA coupling, results in increased right-sided pressures, with right atrial dilatation and increased right atrial and systemic venous pressures (5). This exacerbates pulmonary congestion by reducing clearance of lung water via pulmonary lymphatics. The underlying pathogenesis of HFpEF is still the subject of ongoing research, but pro-inflammatory…

Fig. 4. Echocardiography prior to and post exercise can reveal comparatively subtle increases in diastolic dysfunction. Reproduced here is the case of a 75-year-old male with current exertional dyspnoea and a history of percutaneous coronary interventional therapy. Wall motion analysis revealed no exercise-induced wall motion abnormality in either view (A, B). The measured mitral flow pattern and tissue Doppler was consistent with that of delayed relaxation (C) and E/E’ increased from 14 at rest to 16 with exercise [127]. Similarly, hyperechoic b-lines that arise in the lung from transudated fluid (D) that can be detected in HFpEF patients with dyspnoea, with good prognostic power [128]

Fig. 5. In an “in-magnet” CMR exercise study using a stepping ergometer (A) with whole-heart coverage (B) during 20 W submaximal exercise on a population of patients spanning the spectrum of diastolic dysfunction, it was found that the absolute change in right (C) and left (D) atrial volumes during exercise was highly maladaptive in HFpEF: greater dilation during exercise is suggestive of increased filling pressures [137]

Fig. 6. Patients with increasing diastolic dysfunction progressively dilated atrial volumes, most likely as a result of increased filling pressures as alluded to in Fig. 3. \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${}^{31}$$\end{document}31P-magnetic resonance spectroscopy (obtaining from the mid interventricular septumA spectra showing the presence of high-energy metabolites such as phosphocreatine (PCr), three resonances corresponding to the three \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${}^{31}$$\end{document}31P nuclei in ATP; and 2,3-diphosphoglycerate, B). This subsequently revealed in that these patients a discrete energetic deficit (i.e. a reduction in the detectable PCr/ATP) that was progressively worse across the groups (C). This was accompanied by an increase in detected pulmonary fluid as detected by a…

Fig. 7. Myocardial oxidative metabolism inferred from the kinetics of the PET tracer 11C-acetate, which is visible in the RV and LV before being taken up into the myocardium and later excreted as it decays (A). By fitting these data to an appropriate mathematical model (B), it is possible to estimate myocardial mechanical work (denoted external work, EW) and infer MVO\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$_2$$\end{document}2 and myocardial blood flow (MBF). In a trial of \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$n=19$$\end{document}n=19 HFpEF patients undergoing dobutamine exercise-mimetic stress, it was found that the ability of the heart to augment these values was reduced in HFpEF. This is consistent with an earlier indication in \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym}…