Patterns of dyspnoea onset in patients with acute heart failure: clinical and prognostic implications

Aims Despite attempts to improve the management of patients with acute heart failure (HF), virtually all therapeutic agents investigated in large clinical trials failed to show any consistent reduction in mortality and morbidity. Complexity of the clinical syndrome of acute HF seems to be likely an underlying explanation. Traditionally, clinical trials studied mixed patient populations with acute HF, and only recently, better clinical characterization of patients has been proposed. Dyspnoea is the most common presenting symptom related to hospital admission for acute HF. Whether in patients with acute HF, the pattern of symptoms onset preceding hospital admission is associated with clinical characteristics, and the outcomes have not yet been established. Methods and results We investigated 137 patients (mean age: 65 +/- 13 years; 80% men) hospitalized due to acute HF with dyspnoea as major reported symptom, who were divided according to the time of its onset into those with acute (n = 98) vs. subacute (n = 39) onset (i.e. within 7 days vs. >7 days preceding hospital admission, respectively). On admission, the former group presented higher blood pressure (138 +/- 33 vs. 121 +/- 32mmHg), more often moderate-severe pulmonary congestion (33 vs. 8%), and lower bilirubin level [1.07 (0.72-1.60) vs. 1.27 (0.87-2.06); P < 0.05 in all comparisons]. There were no other differences in baseline clinical characteristics and laboratory indices. Higher percentage of patients with an acute dyspnoea onset reported marked/moderate dyspnoea relief after 6 (18% vs. 7%), 24 (59% vs. 24%), and 48h (80% vs. 46% assessed as an improvement of at least 5 points in self-reported 10-point Likert scale; P < 0.05 in all time points). In patients with an acute onset of dyspnoea after 48h, a decrease of N-terminal pro BNP was more frequently observed (83% vs. 65%), and the levels of endothelin-1 were more reduced [-1.1 (-2.9-0.03) vs 0.4 (-2.2-1.4); all P < 0.05]. Patients with acute onset experienced less in-hospital HF worsening (13% vs. 40%, P = 0.001), and 1 year cardiovascular mortality was significantly lower (20% vs. 41%, P = 0.01). On the multivariable analysis, subacute pattern of dyspnoea was independent predictor of 12 month cardiovascular mortality in patients with acute HF after adjusting for other prognostic factors: systolic blood pressure, urea, and HF de novo [hazard ratio (95% confidence interval): 2.32 (1.13-4.75), P = 0.02]. Conclusions In patients with acute HF, the pattern of symptoms onset is associated with baseline differences in clinical characteristics, biomarker profile, response to standard treatment, and the long-term outcomes. This is relevant information for planning future clinical trials.