102. Nuclear and Multimodality Imaging: Myocardial Viability

CardioNerd Amit Goyal is joined by Dr. Erika Hutt (Cleveland Clinic general cardiology fellow), Dr. Aldo Schenone (Brigham and Women’s advanced cardiovascular imaging fellow), and Dr. Wael Jaber (Cleveland Clinic cardiovascular imaging staff and co-founder of Cardiac Imaging Agora) to discuss nuclear and complimentary multimodality cardiovascular imaging for the evaluation of myocardial viability. Show notes & #Tweetorial were created by Dr. Hussain Khalid (University of Florida general cardiology fellow and CardioNerds Academy fellow in House Thomas). To learn more about multimodality cardiovascular imaging, check out Cardiac Imaging Agora! Collect free CME/MOC credit just for enjoying this episode! CardioNerds Multimodality Cardiovascular Imaging PageCardioNerds Episode PageCardioNerds AcademyCardionerds Healy Honor Roll CardioNerds Journal ClubSubscribe to The Heartbeat Newsletter!Check out CardioNerds SWAG!Become a CardioNerds Patron! Show Notes & Take Home Pearls In response to ischemia the myocardium can dynamically change along a spectrum from myocardial stunning to myocardial hibernation to myocardial necrosis. The goals of viability testing are to identify patients who may benefit from revascularization as hibernating or stunned myocardium are potentially reversible causes of LV dysfunction. There are numerous imaging modalities available for the evaluation of myocardial viability. The broad range of ways in which myocardial viability is assessed speaks to the complexity of the disease spectrum and the difficulty in creating a unifying definition of viability to assess in clinical trials. Five Take Home Pearls 1. In response to an acute episode of ischemia with subsequent reperfusion, the myocardium can be exposed to a large flux of oxygen free radicals or calcium overload that affects the cellular membrane and contractile apparatus. This phenotypically results in decreased contractility of the affected region of myocardium that can persist for weeks, labeled myocardial stunning 2. Repeated episodes of myocardial stunning or chronic low myocardial blood flow can lead to cellular changes such as resorption of the contractile apparatus in order to decrease oxygen demand and allow the myocardial cells to survive. Phenotypically, this might appear as regions of hypokinesis or akinesis at rest with a fixed perfusion defect on myocardial perfusion imaging. This is typically considered hibernating myocardium. 3. The goal of myocardial viability testing is to be able to differentiate between stunned, hibernating and necrosed myocardium. In patients with known epicardial coronary disease, this differentiation allows us to identify who may benefit from revascularization with improved LV systolic function and overall survival. 4. There are several imaging modalities that can be used in the assessment of myocardial viability. The most sensitive modalities are FDG-PET and CMR. The addition of Dobutamine or first pass perfusion with Gadolinium additionally increases the specificity of CMR. These modalities are more expensive and not as widely available. 5. The dynamic nature of the myocardial hibernation and the lack of a unifying definition/phenotypic expression of myocardial hibernation and viability have made it difficult for clinical trials to show that re-establishing myocardial blood flow to hibernating myocardium is beneficial. As Dr. Jaber stated in the episode in his spin on the classic opening phrase from Leo Tolstoy’s masterpiece, Anna Karenina, “All normal hearts are normal in the same way, and all abnormal hearts are abnormal in different ways.” 6. The PARR-2 trial was one of the few randomized, controlled trials of patients with LV systolic dysfunction and coronary artery disease who were randomized to either FDG-PET guided management or standard care with respect to whether to pursue revascularization. Overall, there was not a significant reduction in the primary composite endpoint between the FDG-PET arm and the standard care arm. However, not all patients received the revascularization strategy recommended by imaging. In patients whom the PDG-PET recommendation for revascularization was followed, there was a significant benefit compared to the standard care group. Quotable: “All normal hearts are normal in the same way, All abnormal hearts are abnormal in different ways”—0:54 Detailed Show Notes What is myocardial hibernation and myocardial stunning? How do these concepts fit into the discussion of myocardial viability? A common scenario encountered in clinical practice is the patient who has depressed LV systolic function and known obstructive epicardial coronary disease. For these patients, we may wonder if the myocardium supplied by the epicardial coronary arteries with obstructive lesions is living (viable) or dead(scarred), and whether there would be a benefit to revascularization. If the LV systolic function is decreased with hypokinesis or akinesis and perfusion deficits, then the myocardium is either dead (scarred), stunned, or hibernating! This is a spectrum. Stunned myocardium and hibernating myocardium were originally described in the late 1970s and popularized in the 1980s — stunned myocardium by Dr. Braunwald and Dr. Kloner and hibernating myocardium by Dr. Diamond and Dr. Rahimtoola. When first described, myocardial stunning was thought of as a “hit” (episode of severe ischemia), “run” (relief of ischemia before irreversible injury) and “stun” (a relatively long period of post-ischemia LV dysfunction). What are stunned myocardium and hibernating myocardium? When a region of myocardium becomes ischemic and that ischemia is severe and prolonged, myocardial necrosis occurs, there is no return of contractile function, and the myocardium is replaced by scar tissue. If, however, there is reperfusion and relief of the ischemia before necrosis occurs, the myocardium can become “stunned”. Myocardial stunning is a transient period of post-ischemic dysfunction that can persist for days to weeks prior to recovery of myocardial function. There are a variety of hypotheses as to why this occurs. Some of the leading hypotheses are: In response to ischemia, there can be a flux of oxygen free radicals that disrupt cellular membranes and the contractile apparatus of the cell. Calcium overload that affects myofilament responsiveness to calcium or leads to sarcoplasmic reticulum dysfunction. Phenotypically, this may manifest as hypokinesis or akinesis of the corresponding area of myocardium. If there are repetitive episodes of myocardial stunning or if there is chronic low myocardial blood flow to a region of the myocardium, this can lead to myocardial hibernation. Essentially, the myocardium undergoes metabolic adaptations and downregulation of function (e.g. resorption of the intracellular contractile apparatus) that allows the myocardium to survive by reducing myocardial oxygen demand. Phenotypically, this results in contractile abnormalities at rest that may manifest as hypokinesis or akinesis of the corresponding area of myocardium. This dysfunction may persist weeks to months even after revascularization as the contractile apparatus replenishes. As referenced in the episode, Dr. Rahimtoola popularized the concept of hibernating myocardium in a published report in the 1980s of a patient who had chronic angina, single vessel obstructive epicardial coronary disease in the LAD, depressed LV systolic function, and an anteroapical myocardial wall motion abnormality (WMA). After administration of nitroglycerin, the patients LV systolic function and WMA improved suggesting that this area of the myocardium was viable. The patient underwent coronary bypass surgery and their LV systolic function and wall motion eventually normalized—confirming that this area of myocardium was viable all along. As described by Dr. Kloner in a recent review, an analogy to hibernating myocardium is a broken arm that is casted. As the muscles are not being used, we can expect some atrophy and similarly with hibernating myocardium, the cardiac muscle is not contracting and some level of atrophy is not unexpected. As with a broken arm that is casted will need some time to recover near full function, revascularization will not lead to immediate normalization of cardiac function. What are our goals when it comes to viability testing? In which patients should we pursue viability testing (evaluation for myocardial stunning or myocardial hibernation)? The primary goals of viability testing are: To avoid attempting to revascularize dead myocardium as this would unnecessarily expose them to the risks of an invasive procedure. To identify patients who may have an improvement in LV systolic function with revascularization. To potentially improve survival. There are certain patient populations in whom we should not pursue viability testing as the information provided by testing would not change our management: Patients who have normal coronary arteries or nonobstructive disease. Patients with obstructive epicardial coronary disease that is not amenable to revascularization. Patients with normal LV systolic function. There are different modalities we can use to assess for myocardial viability. How can we conceptualize the different modalities and what are the advantages/disadvantages of each one? We can broadly differentiate the modalities used to assess for myocardial viability into those that are looking for “signs of life” (e.g., evidence of inducible contractility, cell membrane integrity, metabolic activity) and those that are looking for “signs of death” (e.g., myocardial wall thinning, presence of scar). How to look for signs of life: Dobutamine Stress Echocardiography With DSE, we are trying to prove that areas of the myocardium that are hypokinetic or akinetic have some reserve and contractile function.