Background: There is a need for better non-invasive methods to quantify left ventricular (LV) regional myocardial function under different LV loading conditions, particularly in patients at risk for heart failure. Objectives: We investigated the feasibility of non-invasively quantifying these LV functional characteristics at rest and during exercise. Methods: We enrolled 17 patients with hypertension and/or metabolic disorders (9 women, mean age, 46.2 years) and 32 healthy subjects (15 women, mean age, 40.6 years). We recorded LV longitudinal systolic strain (SS) and myocardial velocity during early (E') and late (A') diastole at rest and during increased afterload (handgrip exercise) and central BP by carotid-artery applanation tonometry. Regional myocardial ejection work density (EWD) was the area of the pressure-strain loop during ejection. Mean handgrip force was similar in two groups. Results: In healthy subjects (P < 0.0001 for all), the hemodynamic changes were +13.7 mmHg for end-systolic LV pressure (relative change with exercise [λ], +15.5%), +8.3 bpm for HR (λ+14.2%), +0.56 L/min for CO (λ+12.3%), +1.14% for maximal SS (λ+6.5%; P = 0.03), +131 Pa/m2 for regional myocardial EWD (λ+23.5%), +0.92 cm/s for A' velocity (λ+15.7%), and -0.28 for E'/A' (λ-14.4%). In patients, the corresponding changes were +18.2 mmHg (λ+19.5%; P < 0.0001), +10.8 bpm (λ+18.3%; P < 0.0001), +0.57 L/ml (λ+11.1%; P = 0.0005), and -2.0% (λ-8.8%; P = 0.02), -80 Pa/m2 (λ-8.0%; P = 0.10), +0.47 cm/s (λ+7.2%; P = 0.15), and -0.08 (λ-5.1%; P = 0.38), respectively. P-values for the baseline-adjusted between-group differences were 0.19 for end-systolic pressure, 0.19 for HR, 0.95 for CO, 0.001 for maximal SS, < 0.0001 for segmental myocardial EWD, 0.30 for A', and 0.09 for E'/A'. Conclusion: Using a non-invasive technique involving simultaneous recordings of LV and arterial function, we demonstrated reduced cardiac mechanic efficiency in patients with hypertension and/or obesity but normal ejection fraction. Elevation of systolic load increased atrial-induced myocardial LV lengthening as measured by Tissue Doppler echocardiography.