Abstract Background In heart failure (HF), the Weber and Ventilatory Classes are well acquired landmark reference exercise classifications for quantification of outcome. However, they have not been associated with a thorough hemodynamic phenotyping in the modern HF populations. Methods 194 HF patients with preserved (N=41), mid-range (N=43), and reduced (N=110) ejection fraction and patients with exercise induced-dyspnea and no HF (nonHF, N=77) underwent CPET combined with Echo-Doppler with special attention for the assessment of left atrial dynamics by strain (LAS) analysis, and right ventricular (RV) to pulmonary circulation (PC) coupling assessed by transticuspid annular plane systolic excursion (TAPSE)/pulmonary arterial systolic pressure (PASP) ratio. They were also evaluated in terms of clinical outcome (mortality and HF hospitalization). Results Distribution and variables of interest for Weber Classes were: Class A; n=22 nonHF, no HFpEF, 3 HFmrEF, 3 HFrEF with LAS during exercise of 39±12% and TAPSE/PASP of 0.67±0.21 mm/mmHg; Class B; n=25, 7, 12, 21 with LAS during exercise of 28±14% and TAPSE/PASP of 0.56±0.25 mm/mmHg; Class C: n=27, 25, 20, 48 with LAS during exercise of 24±14% and TAPSE/PASP of 0.46±0.18 mm/mmHg; Class D; n=3, 9, 8, 38 with LAS during exercise of 17±12% and TAPSE/PASP of 0.33±0.14 mm/mmHg and Ventilatory Class I: 59, 24, 22, 39, with LAS during exercise of 31±14% and TAPSE/PASP of 0.55±0.21 mm/mmHg; Class II: 14, 9, 12, 39 with LAS during exercise of 22±13% and TAPSE/PASP of 0.45±0.21 mm/mmHg; Class III: 3, 7, 5, 20 with LAS during exercise of 16±7% and TAPSE/PASP of 0.31±0.09 mm/mmHg; Class IV: 1, 1, 4, 12 with LAS during exercise of 10±6% and TAPSE/PASP of 0.28±0.11 mm/mmHg. Significant differences among each classes in LAS during exercise and peak TAPSE/PASP (P<0.05, respectively) have been observed (Figures A and B). LAS during exercise and peak TAPSE/PASP were positively correlated with peak VO2 (R=0.45 and 0.49, P<0.05, respectively) and also negatively correlated with VE/VCO2 slope (R=−0.49 and −0.55, P<0.05, respectively). Cox proportional hazard regression analyses showed that Weber (HR=3.7, 95% CI 1.7 to 8.0, P<0.001) and Ventilatory Classes (HR=1.7, 95% CI 1.1 to 2.7, P=0.01) were independently associated with the cardiac endpoint after adjustment for age and gender. Clinical stratification according to Weber (A/B or C/D) and Ventilatory (IV or not) Classes clearly differentiated between patients with low and high clinical risk (HR=2.8, 95% CI 1.4 to 5.7, P=0.005, Figure C). Conclusions In patients with HF of any LVEF, Weber and Ventilatory classifications are paralleled by progressive impairment in exercise echo-derived hemodynamic parameters of left atrial function and RV to PC coupling. Peak VO2 and VE/VCO2 slope combine in a strong predictive value irrespective of type of HF.