SPC365

Biochemical and Structural Recovery in HFrEF: Pathophysiological Distinctions and Prognostic Contributions

Session: Sessão de Comunicações Orais 02 – Perspectivas translacionais na Insuficiência Cardíaca: dos modelos experimentais ao prognóstico clínico
Speaker: João Fernandes Pedro

Congress: CPC 2026
Topic: D. Heart Failure
Theme: 10. Chronic Heart Failure
Subtheme: 10.2 Chronic Heart Failure – Epidemiology, Prognosis, Outcome
Session Type: Comunicações Orais
FP Number: ---
Authors: João Fernandes Pedro; João Cravo; Diogo Ferreira; Ana Francês; Fátima Salazar; Nuno Lousada; Joana Rigueira; Rafael Santos; Doroteia Silva; Fausto J. Pinto; Dulce Brito; João R. Agostinho

<p style="text-align:justify"><span style="font-size:10pt"><span style="font-family:Arial,sans-serif"><span style="color:#000000"><strong>Introduction and Aim</strong></span></span></span></p>

<p style="text-align:justify"><span style="font-size:10pt"><span style="font-family:Arial,sans-serif"><span style="color:#000000">Reverse remodelling in HFrEF involves both biochemical improvements, reflecting neuro-hormonal inhibition, and structural changes in ventricular function, yet their relative and independent prognostic roles are unclear. This study evaluated baseline characteristics across recovery phenotypes during medical therapy (GDMT) optimization and assessed the prognostic impact of biochemical versus structural recovery.</span></span></span></p>

<p style="text-align:justify"><span style="font-size:10pt"><span style="font-family:Arial,sans-serif"><span style="color:#000000"><strong>Methods</strong></span></span></span></p>

<p style="text-align:justify"><span style="font-size:10pt"><span style="font-family:Arial,sans-serif"><span style="color:#000000">We retrospectively analyzed 270 HFrEF patients followed for 3 years after GDMT optimization. Patients were categorized into three mutually exclusive groups according to predefined criteria: biochemical recovery only (&ge;50% NT-proBNP reduction </span></span></span><span style="font-size:10pt"><span style="font-family:Arial,sans-serif"><span style="color:#000000"><em>and</em></span></span></span><span style="font-size:10pt"><span style="font-family:Arial,sans-serif"><span style="color:#000000"> follow-up NT-proBNP &lt;1000 pg/mL, without LVEF improvement), LVEF recovery (&gt;10% absolute increase </span></span></span><span style="font-size:10pt"><span style="font-family:Arial,sans-serif"><span style="color:#000000"><em>and</em></span></span></span><span style="font-size:10pt"><span style="font-family:Arial,sans-serif"><span style="color:#000000"> follow-up LVEF &gt;40%, irrespective of NT-proBNP changes) and no recovery (neither criterion fulfilled). Baseline characteristics were compared using ANOVA or &chi;&sup2; tests. Kaplan&ndash;Meier curves assessed 3-year HF event-free survival. Prognostic effects were quantified using univariable and multivariable Cox regression, and incremental value was evaluated by changes in chi-square model.</span></span></span></p>

<p style="text-align:justify"><span style="font-size:10pt"><span style="font-family:Arial,sans-serif"><span style="color:#000000"><strong>Results</strong></span></span></span></p>

<p style="text-align:justify"><span style="font-size:10pt"><span style="font-family:Arial,sans-serif"><span style="color:#000000">Baseline characteristics were similar across groups. Only sex distribution and eGFR differed between groups. Three-year event-free survival varied markedly across phenotypes (log-rank p&lt;0.001). In univariable Cox regression, LVEF recovery was associated with a significantly lower risk of HF events (HR 0.288, 95% CI 0.154&ndash;0.538; p&lt;0.001), and biochemical recovery conferred a similarly strong protective effect (HR 0.244, 95% CI 0.112&ndash;0.532; p&lt;0.001).</span></span></span></p>

<p style="text-align:justify"><span style="font-size:10pt"><span style="font-family:Arial,sans-serif"><span style="color:#000000">When both domains were included simultaneously, biochemical recovery remained independently associated with prognosis (HR 0.309, 95% CI 0.145&ndash;0.659; p=0.002), whereas LVEF recovery lost significance (HR 0.437, 95% CI 0.190&ndash;1.008; p=0.052). Biochemical recovery provided significant incremental prognostic information beyond LVEF recovery (&Delta;&chi;&sup2;=22.4; p&lt;0.001), whereas LVEF recovery added no meaningful improvement over biochemical recovery (&Delta;&chi;&sup2;=3.77; p=0.052).</span></span></span></p>

<p style="text-align:justify"><span style="font-size:10pt"><span style="font-family:Arial,sans-serif"><span style="color:#000000"><strong>Conclusions</strong></span></span></span></p>

<p style="text-align:justify"><span style="font-size:10pt"><span style="font-family:Arial,sans-serif"><span style="color:#000000">Biochemical reverse remodelling emerged as the only independent predictor of outcomes. Interestingly, these findings indicate that neuro-hormonal inhibition, and maybe, appropriate decongestion&mdash; captured biochemically &mdash; is the primary driver of prognostic benefit after GDMT optimization, whereas structural recovery appears later and may be partially mediated by upstream neuro-hormonal improvement.</span></span></span></p>