Discordance between symptomatic, echocardiographic and renal trajectories after SGLT2 inhibitor initiation in heart failure: a landmark analysis of the prospective CaRD registry.

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.