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Discordance between symptomatic, echocardiographic and renal trajectories after SGLT2 inhibitor initiation in heart
Ivana Jurin1, Antonio Hanžek2, Petar Lišnjić3
1Klinicka bolnica Dubrava, Cardiovascular Department, Zagreb, Croatia.
Insights
Sodium-glucose cotransporter 2 inhibitor (SGLT2i) treatment in heart failure patients showed frequently discordant symptomatic, echocardiographic, and renal trajectories. These discordant trajectories, mainly driven by symptomatic changes, were associated with adverse events but had uncertain predictive value.
Area of Science:
- Cardiology
- Nephrology
- Pharmacology
Background:
- Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are increasingly used in heart failure (HF) management.
- Understanding the impact of SGLT2i on symptomatic, echocardiographic, and renal function is crucial for optimizing HF treatment.
- Patient trajectories following SGLT2i initiation can vary, necessitating an analysis of concordance and stability.
Purpose of the Study:
- To quantify the concordance and stability of symptomatic, echocardiographic, and renal trajectories after SGLT2i initiation.
- To examine the association between these trajectories and subsequent adverse events (death or HF hospitalization).
- To assess the prognostic value of discordant trajectories in HF patients treated with SGLT2i.
Main Methods:
- A landmark analysis of 618 adult patients with HF and LVEF <50% was conducted.
- Paired measurements of New York Heart Association (NYHA) class, left ventricular ejection fraction (LVEF), and estimated glomerular filtration rate (eGFR) were assessed.
- Concordance and stability of trajectories were evaluated, and their association with subsequent events was analyzed using Cox regression and Firth logistic regression.
Main Results:
- Discordant trajectories were observed in 59.5% of patients.
- Most classifications remained stable over time (86.6% retained same classification at day 365).
- Non-concordant trajectories were significantly associated with adverse outcomes (aHR 4.27, p=0.004), primarily driven by symptomatic improvement (NYHA class).
Conclusions:
- Symptomatic, echocardiographic, and renal trajectories after SGLT2i initiation are frequently discordant but generally stable.
- Non-concordance is associated with an increased risk of adverse events, with symptomatic changes being the main driver.
- The incremental predictive value of non-concordance in HF patients treated with SGLT2i requires further investigation.
Objectives:
To quantify the concordance and stability of symptomatic, echocardiographic and renal trajectories after sodium-glucose cotransporter 2 inhibitor (SGLT2i) initiation and examine their association with subsequent events.
Methods:
This day-210 landmark analysis included 618 adults with heart failure, baseline left ventricular ejection fraction (LVEF) <50%, and paired New York Heart Association (NYHA) class, LVEF and estimated glomerular filtration rate (eGFR) measurements on days 150-210. Domains were cross-classified rather than treated as equivalent causal components. Repeat classification was assessed by day 365. Death or heart-failure hospitalisation on days 211-365 was analysed with multivariable Cox regression; fixed-horizon Firth logistic regression and continuous, threshold, weighting and co-intervention analyses tested robustness.
Results:
Discordant trajectories occurred in 368/618 patients (59.5%). Among 209 with repeat assessment, 181 (86.6%) retained the same classification (κ=0.74). Outcome status was complete in 576 patients, with 33 events. Non-concordance was associated with the time-to-event outcome (adjusted hazard ratio 4.27, 95% confidence interval 1.61-11.32; p = 0.004); the fixed-horizon Firth estimate was concordant (odds ratio 4.27, 95% confidence interval 1.64-11.13; p = 0.003). NYHA improvement contributed most of the prognostic signal. Adding non-concordance to a conventional baseline model increased the area under the curve from 0.752 to 0.790, but the bootstrap interval for the increment included zero.
Conclusion:
Trajectories were frequently discordant and usually stable to day 365. Their association with events was non-causal, driven predominantly by symptomatic change and of uncertain incremental predictive value.
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