Phasic Arterial Mechanics and Ventriculo-Arterial Dyssynchrony in Heart Failure with Preserved Ejection Fraction: A Systematic Review and Meta-Analysis of Arterial Systole, Arterial Diastole and Pharmacological Phase Restoration

Background/Objectives: Arterial stiffness is usually treated as a scalar load. We instead framed it as a timing problem, defining arterial diastole as compliant reservoir filling during left ventricular (LV) systole and arterial systole as elastic recoil during LV diastole, and we asked whether the two phases were measurably disturbed in heart failure with preserved ejection fraction (HFpEF), and whether pre-specified drug classes could restore them. Methods: We searched MEDLINE/PubMed, Scopus, and Web of Science from inception to 10 September 2026 (3835 records). After deduplication, 2043 records were screened and 376 full texts were assessed, of which 236 met the eligibility criteria and 84 contributed quantitative data. Random-effects meta-analyses used DerSimonian–Laird estimations with Hartung–Knapp–Sidik–Jonkman confidence intervals; the risk of bias was assessed with the Newcastle–Ottawa Scale and Cochrane RoB 2. Results: Compared with controls without heart failure, patients with HFpEF or diastolic dysfunction with preserved ejection fraction had higher carotid–femoral pulse wave velocity (mean difference +1.72 m/s, 95% CI +0.73 to +2.70; k = 16; p = 0.002), higher brachial–ankle pulse wave velocity (+2.24 m/s, +1.38 to +3.10; k = 7; p = 0.0007), a higher augmentation index (+4.51%, +1.36 to +7.65; k = 10; p = 0.010), and a higher cardio-ankle vascular index (+1.00, +0.29 to +1.71; k = 5; p = 0.017). In randomised trials, pre-specified drug classes lowered the heart-rate-corrected augmentation index relative to comparators (−2.18%, −3.51 to −0.85; k = 11; p = 0.004), although this did not persist when ten further eligible trials were added by generic inverse variance (−1.36%, −2.78 to +0.07; k = 15; p = 0.060). They did not change carotid–femoral pulse wave velocity (−0.11 m/s, −0.40 to +0.18; k = 18; p = 0.428), an estimate that became significant when trials at an overall high risk of bias were excluded (−0.21 m/s, −0.41 to −0.02; k = 13; p = 0.036). Reflected-wave transit times did not differ significantly (−5.09 ms; k = 4), and the pooled correlation between arterial stiffness and longitudinal strain was not significant (r = −0.28, −0.65 to +0.20; k = 4; p = 0.162). Heterogeneity was substantial throughout, and 95% prediction intervals included the nulls for five of the six pooled indices, with the single exception being brachial–ankle pulse wave velocity. Conclusions: Arterial stiffness indices were on average higher in HFpEF, with substantial heterogeneity and prediction intervals that included the nulls for five of the six indices; under restrictions of clinically or haemodynamically defined HFpEF, the augmentation index differences lost significance (p = 0.071) while carotid–femoral pulse wave velocity was only marginal (p = 0.050). In randomised trials, the component that responded to current pharmacotherapy was the wave-reflection amplitude and not aortic conduit stiffness; this reduction derived entirely from hypertensive populations and did not survive the inclusion of ten additional eligible trials (−1.36%, −2.78 to +0.07; k = 15; p = 0.060). No analysis in this review demonstrated that the reflected wave was delayed. The phasic framework is therefore presented as an interpretation and hypothesis for prospective testing, and the phasic indices themselves remain critically under-reported.