Abstract-Hibernating myocardium, characterized by reductions in flow and function at rest, has limited contractile reserve in response to increases in external workload. We hypothesized that this attenuation of function reflects an adaptive downregulation that prevents the development of metabolic evidence of ischemia during stress. To test this hypothesis, pigs were chronically instrumented with a proximal left anterior descending artery stenosis for 3 months, resulting in severe anteroapical hypokinesis with reduced resting perfusion (0.78Ϯ0.05 versus 0.94Ϯ0.07 mL · min Ϫ1 · g Ϫ1 in remote, PϽ0.01; and 0.99Ϯ0.08 in controls, PϽ0.05). Open-chest studies confirmed resting dysfunction compared with normal controls (segment shortening 9.2Ϯ2.2% versus 23.5Ϯ1.1%, PϽ0.05). Resting myocardial oxygen consumption was reduced (63Ϯ3 versus 77Ϯ6 L · g Ϫ1 · min Ϫ1 in controls, PϽ0.05), yet lactate consumption was normal. Although subendocardial perfusion failed to increase during graded, intravenous epinephrine infusion (nϭ8), peak segment shortening (to 17.3Ϯ3.1%, PϽ0.05) and oxygen consumption (to 90Ϯ6 L · g Ϫ1 · min Ϫ1 , PϽ0.01) increased from the depressed resting levels. There was no lactate production in hibernating myocardium, and lactate uptake increased during stress (0.7Ϯ0.1 to 1.2Ϯ0.1 mol · g Ϫ1 · min Ϫ1 , PϽ0.05). The absence of metabolic evidence of ischemia was also confirmed during atrial pacing to a rate of 120 bpm (nϭ8). Thus, despite reductions in function and oxygen consumption at rest, hibernating myocardium retains the ability to increase metabolism without the development of acute ischemia. This supports the hypothesis that the downregulation of oxygen consumption and function in hibernating myocardium is an adaptive response that prevents a supply-demand imbalance during submaximal increases in cardiac workload when coronary flow reserve is limited. Key Words: hibernating myocardium Ⅲ oxygen consumption Ⅲ lactate Ⅲ contractile reserve Ⅲ ␤-adrenergic stimulation H ibernating myocardium is characterized by chronic reductions in flow and function that occur in the absence of infarction or subjective evidence of acute ischemia. 1 Although flow is reduced at rest, the myocardium retains the ability to at least transiently respond to increases in external workload. While considerable attention has focused on assessing contractile reserve in hibernating myocardium, the metabolic responses at rest and during increases in the external determinants of myocardial oxygen consumption are largely unknown. In normal hearts, acute transient ischemia causes dysfunction that is accompanied by a rapid fall in high-energy phosphate levels and a switch to anaerobic glycolysis as evidenced by regional lactate production. When moderate ischemia is maintained for hours, however, reductions in regional function match the reduced levels of oxygen delivery. This prevents irreversible injury by reestablishing a balance between supply and demand, a phenomenon termed "short-term hibernation." 2 Although this reverses lactate rel...

These data indicate that variability in contractile reserve in hibernating myocardium is at least partly related to the protocol used for beta-adrenergic stimulation. The blunted steady-state responses to beta-adrenergic stimulation raise the possibility that, like moderate supply-induced ischemia, an exquisite matching between flow and function develops during moderate demand-induced ischemia. This prevents metabolic deterioration in hibernating myocardium but limits contractile function during increases in the external determinants of myocardial metabolism.

Whether initiation of statins could increase survival free of dementia and disability in adults aged ≥75 years is unknown. PREVENTABLE, a double‐blind, placebo‐controlled randomized pragmatic clinical trial, will compare high‐intensity statin therapy (atorvastatin 40 mg) with placebo in 20,000 community‐dwelling adults aged ≥75 years without cardiovascular disease, disability, or dementia at baseline. Exclusion criteria include statin use in the prior year or for >5 years and inability to take a statin. Potential participants are identified using computable phenotypes derived from the electronic health record and local referrals from the community. Participants will undergo baseline cognitive testing, with physical testing and a blinded lipid panel if feasible. Cognitive testing and disability screening will be conducted annually. Multiple data sources will be queried for cardiovascular events, dementia, and disability; survival is site‐reported and supplemented by a National Death Index search. The primary outcome is survival free of new dementia or persisting disability. Co‐secondary outcomes are a composite of cardiovascular death, hospitalization for unstable angina or myocardial infarction, heart failure, stroke, or coronary revascularization; and a composite of mild cognitive impairment or dementia. Ancillary studies will offer mechanistic insights into the effects of statins on key outcomes. Biorepository samples are obtained and stored for future study. These results will inform the benefit of statins for increasing survival free of dementia and disability among older adults. This is a pioneering pragmatic study testing important questions with low participant burden to align with the needs of the growing population of older adults.

Incidental noncardiac findings on CTACs are common in our veteran population. Overall interobserver agreement in identifying these findings between cardiologists and radiologists is fair. Specific guidelines are needed on how CTACs should be read and reported.