No Evidence of Myocardial Oxygen Deprivation in Nonischemic Heart Failure

Abstract

Background—Whether the myocardium in nonischemic heart failure experiences oxygen limitation remains a long-standing controversy. We addressed this question in patients with dilated cardiomyopathy (DCM) using a dual approach. First, we tested the changes in myocardial oxygenation between rest and stress states, using oxygenation-sensitive cardiovascular magnetic resonance. Second, we sought to assess the functional consequences of oxygen limitation at rest by measuring myocardial energetics before and after short-term oxygen supplementation.Methods and Results—Twenty-six subjects (14 DCM and 12 normal) underwent cardiac magnetic resonance imaging at 3 Tesla to assess cardiac volumes, function, oxygenation, and first-pass perfusion (0.03 mmol/kg Gd-DTPA bolus) at stress and rest (4–6 minutes IV adenosine, 140 μg/kg per minute). Signal intensity change (SIΔ) and myocardial perfusion reserve index (MPRI) were measured from oxygenation and perfusion images, respectively. Furthermore, the effect of oxygen supplementation on resting myocardial energy metabolism was tested using 31P MR spectroscopy, measuring PCr/ATP ratios in both groups at baseline and after 4 hours of oxygen via facemask in the DCM group. During stress, there were equivalent rises in rate pressure product in both groups (DCM, 76±15% and normal, 79±9%; P=0.84). MPRI was significantly reduced in DCM (1.51±0.11 versus normal 1.86±0.10; P=0.03). However, there was no difference in oxygenation between groups: SIΔ in DCM 17±3% versus normal 20±2% (P=0.38). Furthermore, at a left ventricular segmental level, there was no correlation between oxygenation-sensitive SIΔ and MPRI (R=0.06; P=0.43). Resting PCr/ATP was reduced in DCM (1.66±0.07 versus normal 2.12±0.06; P=0.002). With oxygen supplementation, there was no change in PCr/ATP (1.61±0.08; P=0.58; Δ=0.04±0.05). There was also no effect of oxygen on systolic function (ejection fraction pre oxygen, 34±1%; post oxygen, 36±2%; P=0.46; Δ 2±1%).Conclusions—Our results demonstrate dissociation between microvascular dysfunction and oxygenation in DCM, suggesting that the impairment of perfusion is not sufficient to cause deoxygenation during stress. Cardiac energetics are unaffected by oxygen supplementation, indicating the absence of relevant myocardial hypoxia at rest. Our study suggests that novel treatments for nonischemic heart failure should focus on efforts to directly target cardiomyocyte function and metabolism rather than oxygen delivery and microvascular function.

Contractile reserve and cardiopulmonary exercise parameters in patients with dilated cardiomyopathy, the two dimensions of exercise testing

“…They also showed peak systolic myocardial velocity (S′) was a strong correlate of VO 2 . Contributing factors of arterial hypoxemia, low hemoglobin levels, and altered peripheral muscle bioenergetics may also play a role in CO in HF, recent studies, however, have suggested no evidence of myocardial oxygen deprivation in nonischemic HF . We were also unable to demonstrate significant oxygen deprivation during exercise as measured by peripheral oxygen saturation.…”

Inorganic nitrate, hypoxia, and the regulation of cardiac mitochondrial respiration—probing the role of PPARα

“…The failing heart itself is energy-starved (57) and characterized by a down-regulation of FAO (1, 57), which may improve the efficiency of O 2 utilization. It was shown, however, that oxygenation was not impaired in the nonischemic failing myocardium (58), and thus therapeutic strategies that enhance oxidative metabolism, including perhaps NO 3 − supplementation, may be of benefit to these patients.…”

Novel cardiovascular magnetic resonance oxygenation approaches in understanding pathophysiology of cardiac diseases

“…Oxygenation‐sensitive CMR, MPRI and MR Spectroscopy were applied by the same group in patients with dilated cardiomyopathy (DCM) . Interestingly, the presence of impaired myocardial blood flow was not linked to myocardial de‐oxygenation in this population.…”