Dr Carolyn Lam: Welcome to Circulation On The Run, your weekly podcast summary and backstage pass to the Journal and its editors. I'm Dr Carolyn Lam, associate editor from the National Heart Center and Duke National University of Singapore. Dr Greg Hundley: And I'm Dr Greg Hundley, Director of the Pauley Heart Center at VCU Health in Richmond, Virginia. Well, Carolyn, the feature article today is really interesting. It's evaluating the evolution of cardiovascular disease associated adverse events in developing countries and It's really fascinating looking at differences between Russia, China, India, and Brazil, but more to come. Don't want to spoil all that. How about we get started with a cup of coffee and discussing some of the articles in the Journal. Dr Carolyn Lam: You bet, Greg. Well, I want to start off with this paper that provides really novel insights into the pathogenesis of hypertrophic cardiomyopathy. Dr Greg Hundley: Carolyn, you're one of the cardiomyopathy experts. Can you give us a little background before we get started? Dr Carolyn Lam: Not sure about expert, but I can sure give you a background. So. Hypertrophic cardiomyopathy remember, is caused by pathogenic variants in the sarcomere protein genes, and that evokes hypercontractility, poor relaxation, and increased energy consumption by the heart and increases the patient's risk for arrhythmias and heart failure. Recent studies show that the pathogenic missense variants in myosin are clustered in residues that participate in dynamic confirmational states of the sarcomere proteins. In today's paper from co-corresponding authors Dr Seidman and Toepfer from Harvard Medical School, authors hypothesized that these confirmations were essential to adapt contractile output for energy conservation and that pathophysiology of hypertrophic cardiomyopathy resulted from destabilization of these confirmations. So they assayed myosin ATP binding to define the proportions of myosin in two confirmational states called SRX or DRX. This was done in healthy rodent and human hearts at baseline and in response to reduced hemodynamic demands of hibernation or pathogenic hypertrophic cardiomyopathy variants. They found that hypertrophic cardiomyopathy mutations that disrupted the physiologic balance of SRX and DRX altered cardiomyocyte contraction, relaxation and metabolism, and conveyed increased risk for heart failure and atrial fibrillation. In fact, a small molecule could restore the physiologic balance of SRX and DRX and improve functional energetic and cellular abnormalities that occurred in hypertrophic cardiomyopathy. Dr Greg Hundley: Very interesting, Carolyn. Well, let me tell you about my paper. It's called The OUTSMART Heart Failure. It's a randomized controlled trial of routine versus selective use of cardiovascular magnetic resonance for patients with non-ischemic heart failure. And it's from Dr David Ian Paterson at the University of Alberta. This is a study from Canada randomizing 500 patients with suspected non-ischemic heart failure to either having a cardiac MRI as the first imaging study or have an echo, and then based on the echo, order an MRI if the physician so indicates. It was an older version of MRIs, so it's a SUNY assessment of function, including the EF, and then delayed enhancement, a technique that again has been available for the past 20 years and incorporates gadolinium contrast. Dr Carolyn Lam: Greg, this is so unfair. I'm an echo person, you're an MRI person, but you get to tell us the results and inject your thoughts. Dr Greg Hundley: No bias. So, Clinical outcomes, Carolyn, you'll be very appreciative, were similar for the two groups of subjects, although the heart failure etiology was more frequently derived in those that received an MRI, whether you're randomized to an MRI first or if you had an echo and they said, "Oh, go get an MRI." The patients with specific heart failure etiologies from imaging had worse outcomes, whereas the heart failu