In this presentation, Demetri Yannopoulos, MD, discusses advanced reperfusion strategies for patients with out-of-hospital cardiac arrest and refractory ventricular fibrillation.
Good morning and thank you for the invitation. It's an honor to be here. My name is Dimitri Giannopoulos, I'm a professor of medicine and emergency medicine and the medical director for the Center for the Station Medicine at the University of Minnesota Medical School isn't my disclosures. I have received funding from NIH and Department of Defense for grants for CpR and resuscitation research, as well as funding from the helmsley charitable trust for cardiac arrest. Here in the state of Minnesota here, I'm going to start talking about the probability of survival for patients with out of the hostel cardiac arrest as a function of time in the upper left corner. You can see here that people that arresting from paramedics. On the top line here, it's been an integral fibrillation presenting rhythm. The probability of survival after 30 minutes has. It's 10%. And if you have no unshakable rhythms, you're in the single digit within 12-14 minutes. The same experience has been published by Koreans. Were age 75 or less. Um So drop declining survival after 10 minutes of CPR with no survivals after 35 minutes. And from the nationals large database of japan people with shock global rhythms and biochemistry. PR which is the best case scenario after 35 40 minutes. They have 0% survival rates. So that effectively is the standard of affairs in the modern station era and standards. Station strategies are inefficient as the duration of CpR increases Survival. His game after 30 minutes of CPR. Even in patients with initial shock of all rhythms, I have the best survival rates. The reason for that is the presence of coronary artery disease. When people do not resuscitate in refractory to shocks, they tend to have significant coronary artery disease. As we published in 2017 in our large cohort, 84% of the people have coronary artery disease. About 70% of them have two or three vessel disease. The predominant vessel involved was lady And 64% of them had acute traumatic lesions in the presence frequently of chronic total occlusion and high syntax course that most of the patients and military patients would receive by passport. In a recent paper published by our group in C. C. I. We present ischemic integra fibrillation as a continuum of ambulatory patients presenting with stemming in on steamy documented by coronary angiography. And we um you can see here survival rates go from A. c. s. almost 98 To resuscitate patients with. We have 73% and 32% for refractory. We have people and never get pulses on the way to the hospital with an average survival of 53%. So 90 80 980 patients were included in this analysis and basically you can see here the probability of presentation as a function of Johnson's score was similar to the syntax score as a dancing is called increases from moderate 100 200 too severe. Um largest area larger areas of the market area are affected. And so the cpr is unable to successfully return engagement in circulation Early on. You can see all the presentations with patients having stems and most me's resuscitated characterizes the Red one. And as Johnson's car increase above 200 predominant presentation is refractory particular fibrillation and the panel on the on the right, you can see the probability of um uh obstruction in different vessels based on the presentation. The role of duration of CPR is of paramount importance. As we showed in the CPR is the only way you can effectively resist the patients after 2030 minutes of resuscitation successfully. This is the papers published by our group in circulation 2020 and you can see in Orange is the outside a heart which is basically the amiodarone lidocaine placebo randomized trial 18 to 75 group. Um that shows that non survival out of the 636 patients, about 300 plus have the six cpr for more than 35 minutes. And none of those people survive compared to the blue bars, which is the University of Minnesota a Cpr program. And so that if patients arrived with 30 to 50 minutes, they have an average cpr survival rate of about 50%. You can see here that survival decreases about 2025% every 10 minutes of additional CPR duration. But the effect can be seen all the way out to about 100 minutes, whereas 15-20% survival. This information led to the arrest Raul which was a phase two single center open labor under mistral published in the Lancet at the end of 2020. The arrest trial was phase two single center. As I said multiple liam s intention to treat and was performed in the metropolitan area of Minneapolis ST paul. The arrest trial was funded by N. H. L. B. I. Was performed under of except under exception from informed consent and it was under the oversight of the FDA under an I. D. E. Was approved by the I. R. B. At the University of Minnesota and it was monitored by an independent H. L. B. I. D. S. And B. The study. Um the randomized patients 18-75 years of age that had failed three shocks in the field and they had to have body morphology uh that Lucas could be applied and they had an estimated transfer time to the D. Or less than 30 minutes upon arrival to the patients were then randomized to either continue hcls hcls or go to the catholic for Eggman facilitated resuscitation. The study and roll only um 30 patients and was stopped by the DS and be early because it reads the pre specified uh stopping early criteria by protocol. Survival was in the hospital discharge was 43% In the early uh facilitators a station in 7% 6.7% in the standard A CLS group and survival at three and six months um was 43 versus zero. And Um with a P value of .0063. The same thing I was sown here that uh the couple of migrant curve. So is that uh patient that survived hostile discharge? None of his patients died subsequently in this randomized trial where only one patient was discharged alive from the hostel in the standard group eventually died from neurological injuries within 100 days. The observations was also um supported by recently presented the trial. This data is um provided here with courtesy of Professor Bell Avec. The The hyper invasive approach in factory out of the hospital cardiac arrest. The prag out of the house. A character study was presented in a. c. c. 20 21. So they enrolled about 256 patients 132 in the standard group 120 for patients in the hyper invasive approach, they allowed for crossover um with allowed for patients in the standard group to receive ECMO if they arrived at the hospital and the physician felt that they were viable and failures of uh ECMO initiation or refusal by the physician to put somebody enigma was considered a crossover to standard group which effectively is a failure of ECMO Um details on the right here. Uh the study was different than the arrest trial because the randomization happened at the scene and uh people were randomized after 15 minutes of failed resuscitation at the scene. Um The study has not been published yet. But the data from the A. C. C. Presentation suggests that the study barely missed the primary endpoint with survivor with CPC one and 280 days. But biological recovery at 30 days was statistically significantly better with hyper invasive approach. And as you can see here with a couple of my year Curve, a. p. value was significant for overall survival up to six months uh intention to treat the favorable outcome. CPC in one and two were significantly higher at patients that he required more than 45 minutes of CpR and effectively even into the standard group four of the six survivors had cross over to the admin group In the P value is .018. The study was stopped early by the S. And D. For benefit uh as well although it means the primary endpoint, um the the S. And D. Felt it was unethical to continue due to the significant differences. So how about combining the arrest and the practice trial? Um The data is providing myself and professional below lava combined the two populations, you can see here that the survival came up to six months um with the whole cohort and then on the right only with IVF patients is very very significant with higher margin for improvement in the ventricular fibrillation cohort with a hazard ratio of 0.54. The combined. That also showed that was the only chance for survival for patients who receive CPR more than 40 minutes. And you can see here in blue is an intention to the population and you can see the difference in survival and us treated in the orange. You can see here that the P value is extremely powerful. Only ECMO can survive patients recipe are more than 45%, minutes of duration. So the other important thing about ECMO treated patient is that most of the surviving patients end up with normal or low normal ejection fraction due to early revascularization. Enigma supporter for the initial insult. The average effort discharge uh In our trial and cohorts of about 350 patients between the University of Missouri is about 43% And all the follow up patients are six months have normalized in particular. Uh left ventricular ejection fraction of about 50-55%. Um contrary to the common belief, ECMO support unloads the left ventricle and decreases the P. D. A. Market works and consumption by about 30% leading to recover in 3 to 5 days. Here is a cohort of patients we turn down in our institution and you can see that at high volume, high flow support the L. B. D. P. Is actually lower country to what is circulating in circles of the heart failure. Uh colleagues of ours and then the stroke work a significant decrease as well as the pressure volume area which is decreased by about a 3rd. 30% with highly significant um values, publication is underway for this. Um So SCP are essential program military components. We represent a very advanced and very organized experience center with about 70 years depth into its operations. What we have learned is that there are important components in order to have a successful program in uh our talk, the cpr initiation protocols and programs are destined to fail unless you have some important components including to them So tiny and sparkles and activation mobilization pathways. To minimize time to calculation is very important. As you know, after 30 minutes of CPR it's minutes of CPR adds about 2-25% mortality rate. Initial ECMO calculation requires skills available to a few sub specialists. Average calculation for the arrest trial was 5-7 minutes. An average calculation by the same highly trained team in the Marriage Department environment was 10-12 minutes as published by Bartosz and clinical medicine at the same time with the lance of publication. The Etna calculation requires X ray support to have higher rates of success and limited complications. Programs that do not use X ray. They have high levels of failed calculations in a lot of vascular complications. Even the fact that intervention coyotes are readily available, skilled in large bore access and can perform current interventions in place swiftly. Intravascular catalyst. It is a group that needs to be included in any programmatic initiatives for recipes are developed. The place for calculation is irrelevant. That can happen in any diy floral capable as a station room cath lab. In any mobile unit ST calculations do not currently work as the french experience has shown recently in a publication which uh a little bit uh decreased enthusiasm for pretty hospital initiation of act more in the streets. This profusion captors are the most important task after calculation to avoid like the skinny and complications. And it is the skill also processed by individual cardiologist and vascular surgeons. CPL related trauma management. Post CpR is critical to survival. Most of these patients have significant injuries that need to be treated city surgery or vascular surgery. I needed to have an efficient calculation process. There is substantial center where there is a central role of cardiology in managing this patient is about the most importance for outcomes to be positive. Team needs to develop expertise in biology, critical care critical care and create a cohesive team to manage these people similar to burn trauma and other critical care expertise. This is unique population that up to till three years ago, I never made it to the hospital and it's very complicated and sick. The three year survival for CpR. This is the first data presented to also from our group You can see here that survivors from ECMO ECPR leave the hospital have similar survival rate about 65%. Um to L that three patients. And in comparison we have bought here brought here data for the transplant population over the same period from the University of Missouri and the grain is the L. Bat population. The additional public health benefit is that over three years we have 32 solid organ transplants and um 32 patients went home with a functioning organ. Because of this program. On the bottom you can see the separation of survivors based on the level of neurological dysfunction or state upon discharge and where they are going to long term facilities or not. So the bottom if you have neurological injury at presentation and you are disposed to attack um you have a 22% survival at six years. But most of the people die with neurological injuries within a year. And the people that survive at six years have normal biological function For people that leave the hospital with cosmological function and they are not disposed to um an attack. The five year survival rate is almost 80%. So what we have learned here is that the duration of CpR of PCP. Our patients stay in the ICU is similar to the Albert population. You can see here in the bottom of the post procedure ICU stays 19 days in 14 days with alva and 13 days with transplant. And in the hospital 26 days 23 days and 18 days respectively. The survival rate obviously is lower. With the CPR 32% in 87% of land, bad in 97% with transplant. Um Overall as a population cardiology has a new life saving therapy and its operational complexity is similar to other expensive lifesaving. Established cardiology programs completely structuring of the delivery of care is needed to make it probably available. I. C. U. Capacity is the true bottlenecks. Since they're these patients have long stays in the hospitals. Any neuro prognostication is possible with high sensitivity for bad neuro outcomes and should limit the average state to free up beds. So ongoing CpR is effectively like free falling. The longer you fall the higher the likelihood of dying especially there is no one to catch. Now we have the CLS but don't forget the prerequisites for successful program which includes high percentage of bystander cpr this path center directed cpr Minimization to act more initiation time and high volume operators with continuity of care during and after ECMO calculation finally and very important in my opinion be T. V. F. Initial rhythm has the highest benefit and gives the highest yield for the resources deployed given the cost uh in the limited resources nowadays with covid an ICU strain limiting the CLS process to the T. V. F. Patients is probably um highly recommended. And I would thank you very much for the opportunity to speak and I will take any questions