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 Greg Hundley, Associate Editor as well, at Circulation, and Director of the Pauley Heart Center in Richmond, Virginia at BCU Health. Dr Carolyn Lam:                Now, we've heard of the PIONEER heart failure trial and that is a sacubitril/valsartan in acute decompensated heart failure. A very important trial, but was powered on the surrogate outcomes. Now, in today's issue though, we're going to hear a little bit more about the clinical outcomes from the PIONEER heart failure trial, a very important paper, a very important discussion coming right up. Greg, what paper do you have to start us off? Dr Greg Hundley:             Carolyn, I've got another favorite of our little discourse, your next Carolyn's Quiz. Except this time it's essay format, so it's open ended questions. And so here's my question to you. What paper addresses an important issue related to hookah inhalation. So Carolyn, do you know a little bit of the origins of hookah and then how does its use compare to e-cigarettes or conventional cigarettes? Dr Carolyn Lam:                Oh, okay. Well at least the quiz wasn't asking if I smoke hookah. Okay, so hookah, that water pipe smoking pipe, fun stuff. I think, is it a Middle Eastern origin? And frankly I don't know of any data to say whether it is better or worse than cigarette smoking. Dr Greg Hundley:             Yeah, you're exactly right. Hookah, it's a longstanding practice, primarily confined to men from the Middle East. But in the 1990s it was introduced with fruit flavored pre-packaged tobacco products and that ignited a sharp uptake of hookah smoking by young women and also men in the Middle East, and then a migration to our western culture. Now, believe it or not, in the United States and in the United Kingdom, hookah has a prevalence of 15% to 25% among university students. And today, twice as many secondary school children smoke hookah as they do cigarettes, and more adults have tried or currently use hookah than electronic cigarettes.                                                 So, what does this article discuss? Well, it focuses on hookah inhalation byproducts, because the charcoal traditionally is used to heat the hookah tobacco in the water pipe, hookah smoke delivers tobacco toxicants and nicotine plus charcoal combustion products, not only carbon rich nanoparticles and oxidants that may destroy nitric oxide and impair endothelial function, but also large amounts of carbon monoxide, a putative vasodilator molecule that will dilate the arteries independent of endothelial dysfunction.                                                 So, this study enrolled three groups of patients. First, there were 30 26-year-old hookah smokers. Second, there were 20 in which the flavored hookah tobacco product was heated electrically, not by the charcoal. And then finally, 15 age matched cigarette smokers who smoked one cigarette. Dr Carolyn Lam:                Wow, what was the result? Dr Greg Hundley:             Unfortunately, nicotine levels increased similarly with all types of smoking. Now, flow-mediated arterial dilation, a marker of endothelial function, did not become impaired after smoking charcoal heated hookah, but instead increased by about 43%. In contrast, flow-mediated arterial dilation decreased by 27% after smoking electrically heated hookah, compared to the decrease after cigarettes smoking. For hookah smokers, vasodilation increased 138% times more than in the other two groups. Therefore, the acute endothelial dysfunction was masked by those high levels of carbon monoxide that are generated from the charcoal. Remember, carbon monoxide is a very potent vasodilator.