The Role of Arterial Stiffness and Central Hemodynamics in Heart Failure

Abstract

Whereas traditional understanding of left ventricular afterload was focused on a steady-state circulation model with continuous pressures and flow, a more realistic concept is emerging, taking the pulsatile nature of the heart and the arterial system into account. The most simple measure of pulsatility is brachial pulse pressure, representing the pulsatility fluctuating around the mean blood pressure level. Brachial pulse pressure is widely available, fundamentally associated with the development and treatment of heart failure (HF), but its analysis is often confounded in patients with established HF. The next step of analysis consists of arterial stiffness, central (rather than brachial) pressures, and of wave reflections. The latter are closely related to left ventricular late systolic afterload, ventricular remodeling, diastolic dysfunction, exercise capacity, and, in the long term, the risk of new-onset HF. Wave reflection may also evolve as a suitable therapeutic target for HF with preserved and reduced ejection fraction. A full understanding of ventricular-arterial coupling, however, requires dedicated analysis of time-resolved pressure and flow signals. This review provides a summary of current understanding of pulsatile hemodynamics in HF.

Rising arterial stiffness with accumulating comorbidities associates with heart failure with preserved ejection fraction

“…This supports the concept of HFpEF as a disease of the vasculature, characterized by augmented aortic stiffness and unfavourable late‐systolic afterload on the ventricle 4–6 . This results in maladaptive ventricular remodelling, elevated LV end‐diastolic pressure (LVEDP), and exercise intolerance, marking the onset of HFpEF 7–9 . A conceptual state of ‘myocardial fatigue’ is hypothesized, in which the energy‐deprived myocardium becomes functionally impaired 10 .…”

“…By studying at earlier time points in the disease process, early changes in arterial compliance, LV remodelling, and LV diastolic dysfunction (LVDD) can be appreciated. It is well recognized that arterial stiffening is a common feature of ageing, 27,28 hypertension, 6,29,30 diabetes, 31,32 and chronic kidney disease (CKD) 33,34 and an independent predictor of cardiovascular events in HFpEF 9,24,26,35,36 . By investigating this collectively, the potential additive effects of such comorbidities on the ventricular–vascular stiffness that underlie HFpEF can be appreciated, as reflected in modern international guidelines.…”

“…[4][5][6] This results in maladaptive ventricular remodelling, elevated LV end-diastolic pressure (LVEDP), and exercise intolerance, marking the onset of HFpEF. [7][8][9] A conceptual state of 'myocardial fatigue' is hypothesized, in which the energy-deprived myocardium becomes functionally impaired. 10 With unceasing arterial afterload mismatch, a transition to irreversible myocardial damage may develop.…”

“…10 With unceasing arterial afterload mismatch, a transition to irreversible myocardial damage may develop. 11,12 This link between HFpEF and arterial stiffness is well documented, 8,9,13,14 but little data exist regarding the early stages of arterial stiffness that precede HFpEF and its impact on LVEDP induced by amassing vascular comorbidities, for example, diabetes mellitus (DM) and hypertension.…”

Profiling the Biomechanical Responses to Workload on the Human Myocyte to Explore the Concept of Myocardial Fatigue and Reversibility: Rationale and Design of the POWER Heart Failure Study

“…The paucity of studies on functional HF may explain why the aetiology of cardiomyopathies remains unknown in > 50% of Associate Editor Jozine ter Maaten oversaw the review of this article Helen Maddock and Prithwish Banerjee are joint senior authors cases, even after cardiac magnetic resonance imaging [4]. It may also explain the sizeable portion of non-responders to disease-modifying therapies, including sacubitril/valsartan, for HF with reduced ejection fraction (HFrEF) where the cause may not be driven by neurohormonal overactivation, but perhaps, a functional imbalance in ventricular-arterial coupling [1,[5][6][7]. More recently, the unexpected cardioprotective benefits of sodium-glucose cotransporter-2 inhibitors (SGLT2i) in both HFrEF and HF with preserved ejection fraction (HFpEF) [8,9], through its pleomorphic action on cardiac energetics, vascular compliance and haemodynamic unloading [10], are not only a testament to our incomplete understanding of HF but also, to the possibility that this heterogeneous syndrome, particularly HFpEF, may also be a disease of the vasculature that provokes a transiently energydepleted overworked myocardium [11][12][13][14].…”