Increased glucose utilization and regional differences in contractile function are well-known alterations of the failing heart and play an important pathophysiological role. We tested whether, similar to functional derangement, changes in glucose uptake develop following a regional pattern. Heart failure was induced in 13 chronically instrumented minipigs by pacing the left ventricular (LV) free wall at 180 beats ·min^-1 for 3 weeks. Regional changes in contractile function and stress were assessed by magnetic resonance imaging, whereas regional flow and glucose uptake were measured by positron emission tomography utilizing, respectively, the radiotracers ¹³N-ammonia and ¹⁸F-deoxyglucose. In heart failure, LV end-diastolic pressure was 20±4 mmHg and ejection fraction was 35±4 % (all P0.05 vs control). Sustained pacing-induced dyssynchronous LV activation caused a more pronounced decrease in LV systolic thickening (7.45±3.42 vs 30.62±8.73%, P0.05) and circumeferential shortening (-4.62±1.0 vs -7.331.2%, P0.05) in the antero/antero-lateral region (pacing site) compared to the infero-septal region (opposite site). Conversely, flow was significantly reduced by approximately 32% compared to control and was lower in the opposite site region. Despite these non homogenous alterations, regional end-systolic wall stress was uniformly increased by 60% in the failing LV. Similar to wall stress, glucose uptake markedly increased versus control (0.24±0.004 vs 0.07±0.01 µmol · min^-1 · g^-1, P0.05) with no significant regional differences. In conclusion, high frequency pacing of the LV free wall causes a dyssinchronous pattern of contraction that leads to progressive cardiac failure with a marked mismatch between increased glucose uptake and regional contractile dysfunction.