Ventriculo-arterial coupling and clinical outcomes in acute heart failure: a systematic review and meta-analysis of multivariable adjusted data

Background

Ventriculo-arterial coupling (VAC) reflects the interaction between ventricular performance and vascular load and is classically assessed using pressure-volume loops analysis. In acute heart failure (AHF), direct assessment of VAC is rarely feasible due to the practical limitations of manipulating loading conditions in haemodynamically unstable patients. Consequently, non-invasive surrogate measures of right ventricular-pulmonary artery (RV-PA) and left ventricular–arterial (LV-Ao) coupling are used in clinical practice. However, the prognostic significance of non-invasive VAC surrogates in AHF, across different follow-up durations, has not been comprehensively synthesized.

Purpose

We aimed to perform a systematic review and meta-analysis of multivariable adjusted data to evaluate the prognostic association of VAC, measured non-invasively, with clinical outcomes in patients hospitalized with AHF, comparing outcomes across coupling strata.

Methods

The primary outcome was all cause mortality (ACM). Secondary outcomes included in-hospital mortality or adverse outcomes. Statistical analysis was performed using Review Manager 7.2.0 (Cochrane Collaboration). Adjusted hazard ratios (aHRs) and odds ratios (aORs) were pooled using random-effects models with Hartung–Knapp–Sidik–Jonkman adjustment when appropriate. Heterogeneity was assessed with I2 statistics. VAC was categorized according to study-specific definitions of coupling and uncoupling. Pre-specified subgroup analyses were performed according to follow-up duration (in-hospital, approximately 12 months, and beyond 12 months).

Results

For RV-PA coupling surrogates, 27 studies including 23.043 patients were identified, of which 14 studies (11.287 patients) were included in the meta-analysis. RV-PA uncoupling was associated with increased in-hospital mortality (HR 2.19, 95% CI 1.08–4.42; p= 0.03), 12-month ACM (HR 2.03; 95% CI 1.44–2.85; p= 0.007; I² = 0%), and long-term ACM (HR 1.67; 95% CI 1.06–2.64; p= 0.04; I² = 56%). Overall, RV-PA uncoupling was associated with a 1.83-fold higher risk of ACM (95% CI 1.46–2.30; p=0.0002, I² = 46%), with no significant differences across follow-up strata (Figure 1A).

Eight studies evaluated LV-Ao coupling (13.456 patients), but only two studies (5.014 patients) were suitable for quantitative synthesis. LV-Ao uncoupling was associated with increased in-hospital mortality or adverse outcomes (OR 1.70; 95% CI 1.29–2.24; p= 0.0002; I² = 0%; Figure 1B).

Nonetheless, heterogeneity in coupling definitions and outcomes limited robust inference.

Conclusions

In patients hospitalized with AHF, ventriculo-arterial uncoupling-particularly RV-PA uncoupling-is consistently associated with increased short-, intermediate-, and long-term ACM. These findings support the prognostic relevance of RV-PA coupling assessment in AHF. Future studies should aim to establish standardized definitions and cut-off values for ventriculo–arterial uncoupling.Figure 1For image description, please refer to the figure legend and surrounding text.