Cool stuff coming in 2015!

I gotta give a shout out to the #FOAMed world.  The last year and a half has been really stimulating, learning from and exchanging with an amazing cohort of peers, all striving towards self-improvement and saving a few extra lives. I’m also really thankful for all those who take a few minutes of their busy days to read or listen to some of the stuff I spew out, and truly appreciate comments and discussion.

Undeniably #FOAMed has made me a better doc, both from the standpoint of learning and inspiration, which is really the fuel behind continuing education. I’ve been involved in organizing events, and in fact, doing so, and the interaction with both the faculty and the participants has been, in and of itself, of immense worth in terms of motivation and a feeling of kinship to a like-minded group, which I think is very important to practicing physicians.

As a consequence of some of these #FOAMed introductions, some good things are in the planning stages for 2015.

Winter: check out BEEM january 26-28 out in Vancouver BC – I can’t make that but really wish I could.

Spring: Two really interesting events in collaboration with l’ASMIQ (Association des Specialistes en Medicine Interne du Quebec – Quebec internists), one being a half day on Shock & Resus (may 30th), and a full day on Lung Ultrasound (may 29th) featuring the grandfather of it all, guru Dr. Daniel Lichtenstein, the one who invented it (well…discovered it, technically). Both take place in Montreal. (Technically this is for ASMIQ members but if anyone is interested, let me know and I’ll see what I can do!)

Of course, CCUS 2015 takes place may 1-3 in Montreal. Can’t miss that. Register at http://www.ccusinstitute.org.

Summer? I’m not running anything, but definitely going to SMACC Chicago. Just go. ‘Nuff said. http://www.smacc.net.au.

Fall: Ken Milne (@TheSGEM) and I will be planning a really cool day combining a critical appraisal workshop and a review of acute care highlights, taking place in Montreal in the fall. Ken will teach us how to learn while being skeptical, and participants should leave with an important skill as well as a headful of practical knowledge. We don’t have a title for this yet but I’ll be sure to let you know! In the meantime be sure to check out Ken’s awesome stuff at http://www.thesgem.com. He keeps it real.

SGEM Ken

 

I’ve also been asked to organize an Ultrasound Simulation Workshop (we are doing an EchoSchockSim in CCUS 2015), which may also happen towards the end of the year.

 

conferences 2015

Ok, so that was just a bit of an update on what’s up in the next year. Hope to meet some of you at these events, do come and say hi!

cheers

 

Philippe

ECMO for Cardiac Arrest: a big CHEER! #FOAMed, #FOAMcc

So a couple of years ago after hearing Scott’s interview of Joe Bellezzo and Zack Shinar (http://emcrit.org/podcasts/ecmo/) I figured this was the future, and promptly got a hold of these guys and got them to present at CCUS 2013 (link to Zack’s lecture below), where their lectures were mind-blowing and instantly made any resuscitationist green with envy, me included.

So just last month, two articles came out in Resuscitation which are highly pertinent and add a lot of legitimacy to the concept of ECMO for CA, one being the CHEER study by Bernard et al (CHEER Study) and the other, a very interesting canadian retrospective observational study by Bednarczyk et al (ecmo arrest canadian).

 

CHEER!!!

First, the CHEER study. Very well done, designed to combine ECMO, mechanical CPR and hypothermia, N=26, so not massive, but given the magnitude of the treatment effect, IMHO highly significant. Very good criteria (18-65, VF) so basically working with patients having a reasonable prognosis (aside from the cardiac arrest…), and their starting point was after 30 minutes of unsuccessful ACLS.

Now, for experienced clinicians out there, it is fairly obvious that at around 30 minutes, we start to get a little discouraged. Maybe not ready to throw in the towel, but we know things are looking dim. And most of those who do get a late ROSC don’t tend to do very well on the long term…

So it takes the CHEER team about 56 minutes to ECMO runtime.  Now, by 56 minutes of no-ROSC, most arrests would have been called. I think that is a key point to underline – the study essentially begins here, at a point where prognosis is no longer that 8-26% “quoted” survival, but pretty close to 0%.

So what happens? 54% of these patients survive to hospital discharge with good neurological recovery. Lets put this in perspective again. They bring back half the people we probably would have given up on…and discharge them home!!!  That’s crazy impressive.

This pretty much correlates with the experience of Zack and Joe (www.edecmo.com), who recently told me the story of a 20 year old diabetic with a K of 9.0 and an arrest of over 45 minutes. Discharge home a week or so later. Completely fine. Back on facebook and skyping with Zack & Joe.

That’s a humbling thing, because in my ED, my ICU, my hands, she’s a goner. 

 

The Canadian Perspective

Ok, so the Bernardczyk article is also really interesting, because it shows that this can be accomplished in a community hospital, and not necessarily only a tertiary care center, and their numbers (albeit retrospectively) are in the same ballpark.

And here is an awesome point of view from their discussion which I completely agree with and ascribe to:

“This (…) challenges our understanding of cardiac arrest as a terminal manifestation of a dis-ease process with treatment options fraught with futility. Rather, for selected patients, cardiac arrest may be better considered anexacerbating symptom of underlying disease with a therapeutic window to effectively restore perfusing circulation while providing definitive therapy.”

 

Thoughts…

So one concern is with bringing back severely neurologically disabled patients. I think the CHEER, the canadian and the japanese data all pretty much refute this. ECMO, particularly paired with hypothermia (probably TTM style now), seems to have remarkable neuroprotective effects, despite prolonged low-flow states. I think we all rarely see patients with 40-50 minute range arrests showing CPC scores of 1…

So why might this occur?  Does the sudden flow reverse some of the vasoconstriction caused by the epinephrine?  I know from discussing with Joe that if they are thinking that the patient is going to ECMO, they will avoid epinephrine. Recent years have clearly shown that the improved ROSC of epinephrine comes at a cost of greater neurological damage, hence equivocal final result of intact neurological survival.

 

Bottom line?

If you’re a resuscitationist, get on board.  Its expensive, but no more than a bunch of other (sometimes dubious or dogmatic) things we do – and the data is there. I’ve been working on my (community) hospital and will not quit until we have it.

What do you need? A cooperating ER chief / ICU chief, and either a cath lab and a vascular surgeon in your institution or in a collaborating neighbourhood one.

…and some cojones.

 

Absolutely love to hear your thoughts, particularly from anyone with ECMO experience!

…this, of course, and more, at CCUS 2015!   http://ccusinstitute.org/Symposium7.html

 

cheers! (pun intended)

Philippe

 

…and here is Zack at CCUS 2013:

http://www.ccusinstitute.org/Video.asp?sVideo=Resuscitation%20Zach

 

Fluids and Vasopressors in Sepsis, Wechter et al, CCM Journal: Anything Useful? #FOAMed, #FOAMcc

A couple of articles on fluid resuscitation worth mentioning. Not necessarily for their quality, but because they will be quoted and used, and critical appraisal of the content and conclusion is, without a doubt, necessary to us soldiers in the trenches.

The first one, Interaction between fluids and vasoactive agents on mortality in septic shock: a multi-center, observational study, from the october issue of the CCM Journal (2014) by Wechter et al, for the Cooperative Antimicrobial Therapy of Septic Shock Database Research Group, is a large scale effort do shed some light on one of the finer points of resuscitation, which is when to initiate vasopressors in relation to fluids in the face of ongoing shock/hypotension.

So they reviewed 2,849 patients in septic shock between 1989 and 2007, trying to note the patterns of fluid and vasopressor therapy which were associated with the best survival.  They found that survival was best when combining an early fluid loading, with pressors started somewhere in the 1-6 hour range.  I do invite you to read it for yourself, it is quite a complex analysis with a lot of permutations.

So…is it a good study?  Insofar as a retrospective study on a highly heterogeneous bunch of patients, I think so. But can I take the conclusion and generalize it to the patient I have in front of me with septic shock? I don’t think so. In all fairness, in the full text conclusion the authors concede that this study, rather than a clinical game-changer, is more of a hypothesis generator and should prompt further study. That, I think, is the fair conclusion.

In the abstract, however, the conclusion is that aggressive fluid therapy should be done, withholding vasopressors until after the first hour.  This is somewhat of a concern to me, since it isn’t uncommon for some to just read that part…

So why is this not generalizable?  First of all, I think that the very concept of generalizing is flawed.  We do not treat a hundred or a thousand patients at a time, and should not be seeking a therapeutic approach that works best for most, but for the one patient we are treating. Unfortunately, this is the inherent weakness of any large RCT and even more so in meta-analyses, unless the right subgroups have been drawn up in the study design.

Let me explain.

Patient A shows up with his septic peritonitis from his perforated cholecystitis. He’s a tough guy, been sick for days, obviously poor intake and finally crawls in. If you were to examine him properly, you’d have a hard time finding his tiny IVC, his heart would be hyperdynamic, his lungs would have clear A profiles, except maybe for a few B lines at the right base. You’d give him your version of EGDT, and he’d do pretty well. A lot better than if you loaded him with vasopressors early and worsened his perfusion. Score one for the guideline therapy.

Patient B shows up with his septic pneumonia, also a tough guy, but happens to be a diabetic with a past MI. He comes is pretty quick cuz he’s short of breath.  If you examine him properly, he has a big IVC, small pleural effusions, right basal consolidation and B lines in good quantity. He gets “EGDT” with an aggressive volume load and progressively goes into respiratory failure, which is ascribed to his severe pneumonia/ARDS, but more likely represents volume overload, as he was perhaps a little volume responsive, but not volume tolerant. An example of Paul Marik’s “salt water drowning.” (http://wp.me/p1avUV-aD) Additionally he goes into acute renal failure, ascribed to severe sepsis, but certainly not helped by the venous congestion (http://wp.me/p1avUV-2J). If he doesn’t make it, the thought process will likely be that he was just so sick, but that he got “gold standard” care. Or did he?

It may very well be that the studied group may include more Patient A types, and less B types, whose worse outcome will be hidden by the “saves” of the As. If you have a therapy that saves 15/100 but kills 5/100 you still come out 10/100 ahead… Great for those 15, not so much for the 5 outliers.

We, however, as physicians, need to apply the N=1 principle as we do not treat a hundred or a thousand patients at a time. I would not hesitate to be much more conservative in fluid resuscitating a B-type patient, regardless of the evidence.

Unfortunately, until trials include a huge number of important variables (an accurate measure of volume status, cardiac function, capillary leak, extravascular lung water, etc), it will be impossible to extrapolate results  to an individual patient.  These trials will, I suppose, eventually be done, but will be huge undertakings, and I do look forward to those results.

So, bottom line?

It’s as good a study of this type as could be done, but the inherent limitations make it of little clinical use, unless your current practice is really extreme on fluids or pressors. What it will hopefully be, however, is an onus to do the highly complex and integrative trials that need to be done to determine the right way to treat each patient we face.

 

thanks!

 

Philippe

 

COMMENTS:

Lawrence Lynn says:

Excellent post. This thoughtful quote should be read and understood by every sepsis trialists!!

“We do not treat a hundred or a thousand patients at a time, and should not be seeking a therapeutic approach that works best for most, but for the one patient we are treating.”

This single quote exposes the delay in progress caused by the ubiquitous oversimplification which defines present sepsis clinical trials. Bacteria (and viruses) generate “extended phenotypes” which are manifested in the host. These phenotypes combine with the phenotypic host response to produce the range of “dynamic relational hybrid phenotypes of bacterial and viral infection”. These hybrid phenotypes are also affected by the innoculum and/or the site of infection (vis-à-vis, your example of peritonitis).

Certainly Wechter et al and the Cooperative Antimicrobial Therapy of Septic Shock Database Research Group should be commended for beginning the process of moving toward the study of the dynamic relational patterns of complex rapidly evolving disease and treatment.

We are excited to see the beginning of the move of trialists toward the study of dynamic state of disease and treatment. However, before they can help us with meaningful results, trialists will need to study and define the range of “the dynamic relational phenotypes of severe infection” and then study the treatment actual phenotypes. This will not be easy as these organisms have had hundreds of thousands of years of evolution writing the complex genotypes which code for the extended of human infection. Sepsis trailists need to be encouraged by clinicians to rise to the task.

The clinicians must actively teach the trialists, (as you have in your post) that we expect trails which help to identity the therapeutic approach that works best in response to the dynamic hybrid phenotype “we are treating”.

The two linked articles below explain the present oversimplified state of the science of sepsis trails and why we clinicians must teach the trailists not to oversimplify and assure that they move quickly toward the study of the actual dynamic phenotypes of severe infection.

http://www.ncbi.nlm.nih.gov/pubmed/24834126

http://www.ncbi.nlm.nih.gov/pubmed/24383420

This is a paradigm shift so we, as clincians, must act to teach trailists this move is necessary. Otherwise we will continue to be left with hypotheses, which, while nice, are not useful at the bedside.

Lawrence Lynn

 

 

Another plea. Please stop embarassing us. #FOAMed, #FOAMcc.

Despite physiological rationale, common sense, and a JAMA article now almost 2 years old, I still sadly see most of my internal medicine colleagues still routinely reaching for (ab)normal saline.

Its embarrassing.

I genuinely feel bad recommending other fluids in consultations, or in the room of a crashing patient asking the nurse to stop the bolus of NS and change it at least to RL, because it is such a ‘basic’ intervention. Prior to the JAMA article, I mostly gave people the benefit of the doubt. Resuscitation isn’t everyone’s field of interest, nor is physiology, so I didn’t feel that necessarily everyone HAD to know this and ascribe to it. I do understand the 10 year time of knowledge translation, but that’s why #FOAMed exists, to try to cut that down.

So please, unless your goal is specifically chloride repletion, take a deep breath and release your grasp on habit and tradition, and embrace physiology (at least to some degree) and stop using NS as a volume expander whether in bolus or in infusion. RL or plasmalyte – although not physiological, at least not as biochemically disturbing as is 0.9% NaCl.

Having said that, let’s keep in mind that human fluid is colloid, whether it includes a cellular suspension (blood, lymph) or not (interstitial fluid), made of a varying mix of proteins, electrolytes, hormones and everything else we know – and some we don’t – floating around. There is no compartment that contains a crystalloid solution.

I’m quite aware that no meta-analysis has shown that colloids are superior, but it likely is just a matter of the right colloid. Resuscitating with crystalloids is kinda like throwing a bucketful of water at an empty bucket across the room. 70-80% spill, if you’re lucky. And the cleanup may be more costly than a few sweeps of the mop. This is evidence based (SOAP, VASST, etc..).

So a plea to all, spread the word. Its a simple switch. Boycott hyperchloremic acidosis at least.

For more details, here’s a link to my earlier post on NS: http://wp.me/p1avUV-5x

cheers

 

Philippe

Bedside Ultrasound Clip Quiz: Abdominal pain and fever! #FOAMed, #FOAMcc, #FOAMus

Saw this poor fellow recently who presented to the ED with fever and abdominal pain. 73 years young. He came to my attention because of borderline BP (95 systolic) and a lactate of 4.5 mmol.

Here is a transverse scan at his lower right costal margin:

 

What do you think?

Turns out he had been having pain for about two weeks, and it had intensified about two days ago. His wife dragged him in.

What would you do?

 

 

 

 

 

 

 

 

 

 

 

This is septated fluid collection around the liver.  With the fever and history, sounds pretty suspicious for a septic source. After carefully scanning in all angles and watching for a while to make sure this wasn’t a strangely placed loop of bowel, a 22g needle aspiration showed cloudy bilious fluid and a trip to the OR a couple of hours later revealed a perforated duodenal ulcer.

He made it ok.

 

cheers

 

Philippe

Bedside Ultrasound: Quite a Case! #FOAMed, #FOAMcc

So here is an awesome clip from an ICU colleague of mine, Lorraine Law.  She was managing a post arrest (elderly woman who collapsed at home and was resuscitated but remaining in profound shock) case using bedside ultrasound and came across this pathology:

video courtesy of Lorraine Law & Shirish Shantidatt

what do you think?

scroll below for my thoughts…

 

 

 

 

So the clip starts with a subxiphoid 4 chamber view that clearly shows a massively dilated RV with a hyperdynamic and underfilled LV.

[For the hemodynamic novices, remember that the ventricles are kind of like roommates who share a pericardium. Especially in acute scenarios, if one gets overloaded, the other will have to give way, until the pressure equilibrates. If the process is exceedingly slow, they can do some renovations and stretch the pericardium, but this takes likely weeks. In this case, the elevated PAP overloads the RV and the RVDP > LVDP, resulting in decreased diastolic filling, which in turn drops the stroke volume/cardiac output/MAP.]

We can see that the RV TAPSE (tricuspid valve excursion towards apex) is really minimal, supporting an acute or acute on chronic process.

The clip then shows a long axis view of the IVC with echogenic material, most likely thrombus, with a to and fro motion, going in and out of the RA. Wow. You don’t see this very often.  The only thing preventing further travel is actually the fact that the cardiac output is so low due to massive embolism so that the flow can in fact barely carry the clots forward anymore at this point, similar to the sluggish IVC clip I put up a few months ago (http://wp.me/p1avUV-5t).

The most likely diagnosis is pulmonary embolism, and thrombolysis is indicated. Unfortunately despite my colleague’s timely diagnosis, the clot burden was likely too much, and despite thrombolysis, the patient passed away of intractable shock.  One can imagine that the TPA actually has to make it to the lungs, and with such a degree of obstruction, it is likely that very little actually got to the pulmonary vasculature…

Unfortunate case, but quite impressive images.

A crazy thought, using hindsight and with the luxury of knowing the fatal prognosis: intracardiac (RV) TPA bolus? Small spinal needle?  Anyone bold enough? Food for thought if (when) I see one like this…

 

cheers!

 

Comments:

Marco says:

Really quite impressive images. A couple of weeks ago I admitted a pretty young patient after a successful resuscitation due to massive pulmonary embolism. Immediately after ROSC in emergency department, he was transported to the cath-lab where TPA bolus was administered directly through a PA cathether. In ICU we continued the infusion. In less than 24 hours we obtained a relative hemodynamic stability and discontinued all the vasopressors, but the case remains unfortunate because despite therapeutic hypothermia the post-anoxic damage was so severe that led to cerebral death declaration two days later.

 

Thanks Marco, very interesting.  There is a recent study on catheter directed thrombolysis in PE reviewed at PulmCCM:(http://pulmccm.org/main/2014/randomized-controlled-trials/catheter-directed-thrombolysis-submassive-pe-better-heparin-rct/)

A physiological point about PE resuscitation is the relative inefficiency of CPR, as both venous return and LV filling is severely limited, so systemic perfusion is even worse than the usually poor output during chest compressions…

Thanks for reading!

Marco replies:

Thanks, Philippe!
The point about the possible inefficiency of CPR is crucial in my opinion. The patient I brought as example had a witnessed cardiac arrest (he called EMS when in respiratory distress) and CPR without interruption from the beginning, nevertheless he resulted in brain death declaration.
I remember very clearly a 43-year-old woman that 3 years ago had a massive PE in the OR shortly after a long lumbar vertebral stabilization. We admitted her to ICU after more than 80 minutes of CPR, a bolus of rTPA and with severe hemodynamic instability. RV was extremely dilated. When she eventually regained stability I had little hope about her neurological recovery, but surprisingly she was extubated the following day and last year she returned to our 12-months post-ICU follow-up showing perfect recovery.
I think that systemic and cerebral perfusion during “obstructive” cardiac arrests such as massive PE is very difficult to asses with current technology. A couple of times I was tempted to check it with trans cranial doppler, but usually there’s too much confusion during CPR.
When I was a resident I witnessed to a iatrogenic cardiac arrest in a patient with advanced monitoring that led to an interesting publication: http://www.researchgate.net/publication/10832333_Cerebral_perfusion_pressure_and_cerebral_tissue_oxygen_tension_in_a_patient_during_cardiopulmonary_resuscitation

 

Wow, very interesting cases.  What fortune to have been able to record that data, as obviously getting that in during CPR would be almost impossible.  TCD, at least after ROSC, could be contributory… Another option is using NIRS, which I’ll be working with this summer.

thanks again!

Philippe

An Update on Pulmonary Embolism: NEJM’s PIETHO Study…what’s the verdict? #FOAMed, #FOAMcc

As has been discussed in a previous post (http://wp.me/p1avUV-7T), patients with sub-massive PE (hypoxic, tachycardic, some troponin rise, etc…but no hypotension) remain in a grey zone, which is, to me , a dubious situation at best – their mortality can be up to 15%, morbidity likely more.  Everyone agrees the low-risk patients don’t need thrombolysis, and everyone pretty much agrees that the patient in shock needs it.  There is data out there suggesting that some patients clearly benefit from thrombolysis despite not being in shock, in good part relating to avoiding chronic pulmonary hypertension and its consequences.

The issue for many clinicians is that they have a “stable” patient in front of them, and they are considering giving them a drug that can potentially give them a bleed in the head and leave them dead or crippled. Many shy away from this. Part of this is cultural, because the same docs probably wouldn’t hesitate giving the drug to a lateral or posterior MI, which is not likely to kill you, or even leave you a cardiac cripple (just to be clear, I’m not advocating against thrombolysis in these cases, just trying to find a parallel), but since the AHA guidelines say to do it and everyone else does it, there’s no trepidation. It is the standard of care.  For most of us acute care clinicians who do not do outpatient medicine, if the patient survives and gets discharged home, chalk one up in the win column. But, as has become clear in recent years with the post-critical illness syndromes, morbidity can be just as important as mortality, especially in the younger patients. Kline et al (Chest, 2009) showed how almost 50% of “submassive PE” patients treated with anticoagulation alone had dyspnea or exercise intolerance at 6 months. They only had a 15% improvement in their pulmonary artery pressures (mean 45 mmhg).

What are the real risks? Pooling the data together gives a value around 2% with a spread between 0.8% and 8%, more or less. This represents each patient’s inherent risk of bleeding, as well as some of the inconsistencies with post-thrombolysis anticoagulation (safest to aim for 1.5-2 x PTT baseline in the first 48h).

The MOPETT trial which, as a #FOAMite you have certainly come across, showed that a half-dose of TPA was highly effective, and they felt it might be possible to go lower. The physiological beauty in that is that, unlike other sites we thrombolyse with full dose TPA, the lungs get 100% of the TPA (coronary artery gets maybe 5%, brain gets 15%).  Mind you, of course, the culprit clot/artery obviously doesn’t get 100%, but much, much more (if we figure that you need about 50% vascular area occlusion to cause RV dysfunction) TPA per “clot” than other pathologies. One can argue that anatomically, there is a greater clot burden than coronary or arterial thrombolysis, which may offset this somewhat. However, the date was quite clear in this trial that the therapy was effective, and the bleeding was none.

Ok, so let’s get to the PIETHO. 1000 patients, TPA+heparin vs heparin alone in normotensive but intermediate risk patients. So, first question is how was that risk defined?  Patients needed to have echocardiographic/CT signs of RV dysfunction AND a positive troponin. Interestingly enough, onset of symptoms was up to 15 days before randomization…not exactly early treatment, and unfortunately there is no information about the actual time to thrombolysis or subgrouping.  The results were as one could imagine. The combined endpoint of death or hemodynamic decompensation was 2.6% in the thrombolytic group vs 5.6% in the anticoagulation.  I’m not a fan of combined endpoints. Hemorrhagic stroke was 2.0% vs 0.2%. Their conclusion? Exercise caution. Hmmm…not much of a step forward. Basically tells us what we know. It helps the hemodynamics, but you can bleed. They do re-affirm that bleeding is more likely in the over-75.

 

What do we REALLY need to figure out? 

1. echographic risk stratification – at least into moderate and severe RV dysfunction.

2. longer term outcomes (hopefully PIETHO has a follow-up study in the pipeline, since they had good numbers).

3. a point-of-care study – time is of the essence, and may have an impact on dosage. IMHO thrombolysis should be done within a few hours of presentation at most.

4. further dosage data – 1/2? 1/3? 1/4? small boluses q1h until RV function improves?

I wish I could do it, but community hospitals don’t have the ideal setup, nor do I have a research team that can handle something of this scale. But surely someone can!

 

Bottom line?

It won’t change my practice. I will continue to offer thrombolysis in select cases, especially the younger patients, who obviously have a lower risk of bleeding, and stand to benefit the most, as pulmonary hypertension  can be crippling. I know I’d take the risk of bleeding when I see 50% dyspnea/exercise intolerance two years down the road…

Finally, bedside ultrasound to anyone with dyspnea/hypoxia should be a standard of care for every acute care physician. No ifs, ands or buts, no exception. Waiting for a CT angio or formal (read daytime hours) echocardiogram is, to me, unacceptable. If you, a friend or family member were in that ER bed, would you trust a physical examination and a CXR to rule out the need for an immediate intervention? I wouldn’t, not my own, and not even Dr. Bates’, Dr. DeGowin’s or Dr. Sapira’s, or all three combined.

cheers!

 

 

 

Kline JA, Steuerwald MT, Marchick MR, Hernandez-Nino J, Rose GA. Prospective evaluation of right ventricular function and functional status 6 months after acute submassive pulmonary embolism: frequency of persistent or subsequent elevation in estimated pulmonary artery pressure. Chest 2009;136:1202e1210.

Guy Meyer, M.D., Eric Vicaut, M.D., Thierry Danays, M.D., Giancarlo Agnelli, M.D., Cecilia Becattini, M.D., Jan Beyer-Westendorf, M.D., Erich Bluhmki, M.D., Ph.D., Helene Bouvaist, M.D., Benjamin Brenner, M.D., Francis Couturaud, M.D., Ph.D., Claudia Dellas, M.D., Klaus Empen, M.D., Ana Franca, M.D., Nazzareno Galiè, M.D., Annette Geibel, M.D., Samuel Z. Goldhaber, M.D., David Jimenez, M.D., Ph.D., Matija Kozak, M.D., Christian Kupatt, M.D., Nils Kucher, M.D., Irene M. Lang, M.D., Mareike Lankeit, M.D., Nicolas Meneveau, M.D., Ph.D., Gerard Pacouret, M.D., Massimiliano Palazzini, M.D., Antoniu Petris, M.D., Ph.D., Piotr Pruszczyk, M.D., Matteo Rugolotto, M.D., Aldo Salvi, M.D., Sebastian Schellong, M.D., Mustapha Sebbane, M.D., Bozena Sobkowicz, M.D., Branislav S. Stefanovic, M.D., Ph.D., Holger Thiele, M.D., Adam Torbicki, M.D., Franck Verschuren, M.D., Ph.D., and Stavros V. Konstantinides, M.D., for the PEITHO Investigators*, Fibrinolysis for Patients with Intermediate- Risk Pulmonary Embolism, N Engl J Med 2014;370:1402-11.

Mohsen Sharifi, MDa,b,*, Curt Bay, PhDb, Laura Skrocki, DOa, Farnoosh Rahimi, MDa, and Mahshid Mehdipour, DMDa,b, “MOPETT” Investigators, Moderate Pulmonary Embolism Treated With Thrombolysis (from the “MOPETT” Trial), Am J Cardiol 2012