Monday, December 2, 2013

Women, ACS, and "atypical" symptoms - new study


I was excited to read the new study "Sex-Specific Chest Pain Characteristics in the Early Diagnosis of Acute Myocardial Infarction." My excitement was tempered when I saw Ryan Radecki's take on the article, however.  

"Fundamentally flawed" - ouch.

True, the study by Gimenez et al. cannot prove, because of study design, that men and women have similar rates of atypical symptoms of ACS. However, I’m not sure that this makes the study fundamentally flawed, let alone “comical.” It’s too easy to criticize a study for not being a highly-powered, well-controlled (yet externally valid!) “gold-standard” investigation. But how do we proceed until that rare trial is conducted? In the meantime, why not analyze this study on its own terms? 

Most importantly, this was a prospective study of undifferentiated chest symptoms. Too much of the literature that is cited on this topic uses registry data, or only enrolls patients with confirmed ACS, or interviews subjects long after the onset of symptoms. While the study by Gimenez et al. may not be perfect, its methods are far more robust than most other literature in this area. Importantly, the results triangulate well with other kinds of evidence out there.

1. In most diseases, women have the same symptoms as men. 

How many other diseases are said to show a gender-based difference in presentation? Not many, it seems - I’m pressed to come up with another example where the literature even suggests a significantly different symptom complex.


Indeed, many studies point to the absence of differences in various condition. For example, men and women with pulmonary embolism seem to have similar rates of various symptoms. Interesting, since PE often produces the same sort of vague, poorly localized symptoms as ACS. Along the same vein, at least one study suggests that pancreatitis presents much the same in women as in men

Well, instead of symptom differences in heart attacks, how about “brain attacks?” Again, it seems that there are few clinically significant differences in the way men and women describe their stroke symptoms.

Even in appendicitis, a condition that manifests in protean ways, and involves anatomy that sits right next to gender-defining organs in the pelvis, it seems that women have pretty much the same symptoms as men!

So, if there are few (no?) other conditions in which men and women are understood to have clinically significant discrepancies in their symptoms, why should we believe that heart disease should be the rare (sole?) exception?


2. Evidence from the cath lab suggest men and women have similar symptoms. 
Balloon occlusion during PCI is, essentially, a temporary MI. The lumen is occluded for however long it takes to open the artery and deploy the stent, and people can have significant ischemic symptoms during this period. This makes for a great study setting - although we aren’t studying symptoms associated with ACS sensu strictu, we are able to prospectively survey the patients about their symptoms not only after artery occlusion, but before and during as well.

A team in Japan did just that, and found that men and women had chest pain-free occlusions at about the same rate, 35%. Another study, in Canada, also found no difference between men and women in the cath lab.


3. Many studies in this area are not designed to address the crucial question. 
Most of the data looking at men’s and women’s symptoms in ACS come from studies that enrolled patients with confirmed ACS. For example, in the Gimenez et al study, they cite a number of studies that suggest that women present with atypical symptoms more often. Unfortunately, Goldberg 1998, Goldberg 2000, and Dey 2009 all examined only patients with diagnosed ACS. As such, they can answer the question “In patients with an existing diagnosis of ACS, do women and men have different symptoms?” They cannot speak to how to approach the patient with undifferentiated chest pain. 

For example, many of these retrospective studies find that women describe back pain somewhat more often than men. But, what if women without ACS also describe back pain more often than men? If this were the case, back pain would not really be useful as an “atypical” symptom. 

It's worth pointing out that one of the few prospective studies, looking specifically for atypical symptoms in men and women, found that women presented typically more often than men!

Wrapping up...
So, while this study may not be the last word on the subject, it provides yet another high-quality element of evidence pointing towards the same conclusion: Both men and women - old and young, diabetic and not - can have typical or atypical symptoms of ACS.

Sunday, July 21, 2013

Lime's Disease - some underappreciated elements.

This is not meant to be a comprehensive review of B. burgdorferi, the life cycle of I. scapularis, or all the other stuff that belong in a thorough introduction to Lime's disease. Instead, I just want to highlight a few aspects that seem to have been under-appreciated.

First, an exacting review of the anatomy of I. scapularis...

This depiction is actually more realistic than how some CT politicians view ticks and Lyme disease.

#1 The "bulls-eye" rash, while classic, is uncommon.
Anytime a sign is described as classic, you ought to expect that you basically will never see it. My rule of thumb when being pimped about how often you see a "classic sign" is to reply "Well, recent research, ah, I believe, shows a lower rate in the modern era, ah, about 15% I believe."


And the literature on erythema migrans (EM) backs me up. While bulls-eyes, or central-clearing, may have been more common years ago, when it took weeks to diagnose, a study from 2002 found that only 9% of confirmed EM had central clearing. Instead, the majority either were homogenous, or were darker centrally!



 In fact, central clearing occurred at the same rate as rashes which had vesicles or a blue center.

So, all these are erythema migrans:
Central vesicles (source)
Central raised punctum (source)
Triangular, rather than round (source)

What should you look for, if not a bull's eye? A blanchable erythema that is flat, with non-raised border. It should also be large, and rapidly expanding (20 cm2/day).


#2 Don't routinely get "Lyme tests."
The patient lives in suburban Connecticut, it's July, they describe "flu-like" aching and chills, and you find a 15 cm diameter homogenously erythematous rash on their back. You're done - 2 weeks doxy 100 BID, and go see the next patient!

But we're always getting tests. We order BNPs on patients who are on BiPAP and getting 400 µg/minute of nitro, we get a troponin on the patient being rushed to the cath lab for anterior "tombstones," we get a white count in, well, everyone. So why not order a test for Lyme?

Because they don't work well. Some of the pitfalls are:
  • In early localized disease (i.e. EM) about 50% of patients will not yet have a rise in IgM levels.
  • About 5% of the population can  have a positive ELISA test at any given time.
  • In the absence of a supportive history or clinical signs, a positive IgG just indicates past exposure.
  • Elevated IgG, and even IgM, levels can be seen for a long time after successful treatment.
If the rash is equivocal-looking, you can get active and convalescent assays, but this is not routine, and should require discussion with the PMD.

And I enjoy trying to page PMDs almost as much as I enjoy this new yogurt flavor!

#3 Lyme carditis
An otherwise healthy 35 y.o. male comes to the ED with severe presyncope, after having been found to have a heart rate of 30 in the walk-in clinic. He admits to having been told by a coworker at his landscaping job that he had a big red rash on his back 3 months ago (in July), but he never saw it himself. The blood pressure is 80/40, and the ECG shows a complete heart block with a narrow QRS.

How bad is this? I mean, complete heart block - yikes. What should we do right now? Does he need a permanent pacemaker? Will the echo show a nasty cardiomyopathy? How bad is the mortality?

Ok, in order:
  1. Not that bad. These blocks usually last under a week, once antibiotics have been started.
  2. Not a question... But AV blocks are very common in Lyme carditis - about 50% of patients.
  3. Put on pacer pads, order some ceftriaxone, and don't let him walk to the bathroom!
  4. Unlikely. Permanent conduction defects are rare, even though some folks need temporary pacing.
  5. Maybe in the short-term there can be some "reduced squeeze," but the long-term prognosis is very good.
  6. Almost unheard of: a recent review only found two case reports that plausibly link a death due to Lyme disease
Lastly, atropine is not felt to do much, good or bad.


#4 Prophylactic Doxycyline
If a deer tick has been for at least 36 hours, and the patient can take antibiotics within 72 hours after tick removal, and we're in Connecticut (i.e. Lyme endemic area), the the patient should get doxycyline 200mg PO once.
There are a few wrinkles in this, however. For example, you can't do this for kids - there is no data for prophylactic-dose amoxicillin. 

But most importantly, you have to know the risk-benefit numbers. First, what is the risk of developing erythema migrans after a tick bite, and how much does doxy help? The key NEJM study found:


It looks like most deer tick bites, even in Westchester, NY (a Lyme endemic area), do not result in EM. The risk tops out at about 10% for a somewhat engorged nymph, and plummet for the other categories. The one-time dose of doxy drops that rate down to a little over 1%. That's a pretty decent benefit.

Well, how about the risks of prophylactic dosing? 


A 6% risk of vomiting, and 7% abdminal pain? Hmm.

So, another way of looking at it, the patient potentially has a 90% chance of having nothing happen (if no prophylactic dose), versus a 6% chance of being sick as a dog from the doxy. That's the choice!

The Bottom Line
There's a big fear about Lyme disease in Connecticut, and plenty of people work hard every day to make sure that the paranoia doesn't die down.

Like one of our senators, who investigated and sued the Infectious Disease Society of America
(spending at lot of CT tax money in the process), and was ultimately 100% in the wrong. ***
So, as an emergency doctor in this wacky state, you should know this disease pretty well, so you can identify and treat "Lime's disease" appropriately. You can download the excellent IDSA guidelines for definitive information, or check out the CDC website for clinicians as well.

___________________________________________________________
***  My own political views are not represented here, just a medical perspective. So, in order to balance out my criticisms of a Democrat, let me point out that no political party has a lock on pandering to the "chronic Lyme" folks. To highlight a recent example:


He planned to "improve synergy" in treating Lyme. Cool.


Friday, March 29, 2013

Symptoms in men & women during PCI ballon occlusion

The trouble with "chest pain" is that it's, well, pain. The experience is subjective, bound up in the context of prior experience, current emotional state, and comorbidities, as well as the actual nociceptive stimulus. 

Not Garfield.
Frankly, this complex topic does not get any simpler when we consider the question of whether men & women report significantly different symptoms during ACS

First off, I harbor some skepticism about whether such a significant difference exists at all. For all the talk of "men present typically, women present atypically," there isn't a great deal of evidence that women have substantially different symptoms with pancreatitis, pulmonary embolism, CVA, or even appendicitis. Why should the heart be such a radically different organ? 

Nonetheless, the latest big study on the subject suggested that the rates of "chest pain-free" MI are different between the genders: 31% of males versus 42% of females. However, this was a registry study, with all the usual limitations, and so questions remain. But what can you do? It's not like you can take a group of women, a group of men, give them both MIs, and record their symptoms...

Or can you?

"Gender Differences in Symptoms During 60-Second Balloon Occlusion of the Coronary Artery"
Well, sort of.

Japanese researchers decided to approach this issue prospectively. They enrolled 110 men and 80 women who were scheduled to have PCI for stenting of a single stenotic native coronary artery. None of these patients were having any active symptoms (let alone a STEMI) prior to undergoing PCI. They figured that since the balloon inflation required to deploy the stent causes, essentially, a transient total occlusion, it might prove to be a good model for demonstrating the different symptom expression between genders.

The men and the women were fairly well matched, with the exception that the women were, on average, older than the men. The rates of comorbidities, as well as the target vessels, were similar, however.

 

The duration of balloon inflation during the PCI was standardized at 60 seconds, and the patients were interviewed immediately after balloon deflation for:
"presence or absence of the following symptoms during the balloon inflation: chest pain, toothache, jaw pain, neck/throat pain, shoulder pain, upper or lower arm pain, epigastralgia, occipital pain, back pain, dyspnea, nausea, and vomiting."
The first interesting point is that not everyone had chest pain when the balloon was inflated. In fact, 38/110 men (35%) and 28/80 (35%) women had no symptoms at all.

So, the genders were evenly matched for "pain-free" coronary occlusion. What kind of symptoms did the remaining 65% of men and women have?


Surprisingly, essentially all the men and women reported having "chest pain." When asked about additional symptoms, however, women reported more of the "non-chest" symptoms than did the men, although none of the individual elements reached statistical significance.

To summarize: Men and women had the same rate of symptom-free coronary occlusion, and the same rate of chest pain. Women had more symptoms on top of that chest pain, however. The researchers concluded, nevertheless, that:
[N]on–chest pain symptoms during the 60-second balloon occlusion of the coronary artery were more common in women than in men, supporting the presence of the gender difference in myocardial ischemic symptoms.
Discussion
I think we're making a mistake by focusing on a putative 11% difference in "typical" chest between genders, and should instead remind ourselves that 31% - 42% of patients with ACS do not have a typical presentation. In other words, the variation in symptoms between genders is dwarfed by the range of presentations within either gender.

Furthermore, the present study suggests that the difference in symptoms between men and women, when examined in a fairly well-controlled setting, may be trivial. These results are similar to those obtained by a Canadian group in 2011. Those researchers also employed a PCI setting to record patients' descriptions of symptoms during inflationOverall, they also found no significant difference between the genders.


Now, what do EM residents really want from the review of a new study? They want to know - Can you use the results of this study in the ED tomorrow? And the "trick answer" is that no special gender-based strategy is need or even helpful
 Just be concerned about ACS in everyone!




Wednesday, December 12, 2012

It's narrow, regular, and fast - Now what?

Despite the variety of disorders an illness that parade through the ED, it often seems like each shift has a "theme." For example, you may diagnose two ectopic pregnancies in one shift, or send 3 patients to the cath lab. 

Heck, on a rare day you may actually have 3 or 4 patients with alcohol intoxication!

This is a thing that happens. Source

Last week for example, the theme for Yuko & I was narrow-complex tachycardias. As themes go, this was a good one - quick procedures, no untoward events, and we made the patients felt better!

Mrs Black
An older lady, Mrs Black had felt palpitations start about an hour before she arrived in the ED. Although she had no chest pain or pressure, she admitted to a little shortness of breath, as well as mild nausea. She took a variety of medications for hypertension, but no calcium-channel blockers or beta-blockers. Her vitals were normal.

Her first ECG:


Mrs. Black - before

After 6 mg of adenosine, we had:


Mrs. Black - after

Mr White
Our next PSVT came in only 2 hours later.

Also elderly, Mr White had been having some mild racing of his pulse over the past week, but the symptoms acutely worsened about 3 hours prior to coming to the ED. He had used a home-BP machine and noted that his systolic pressure had only been 70 at one point. The ED tech, of note, mentioned that he had looked fairly ill at triage - pale and sweaty.

His first ECG:


Mr White - before

And again, after 6 mg of adenosine (I'm not very original):


Mr White - after

So what's going on?
Ok, they're both narrow-complex tachycardias, very regular, with rates well under 150. So atrial fibrillation and flutter are pretty unlikely, as is a sinus tachycardia.

So that leaves the somewhat broad category of PSVT. Now, we usually just leave it at that in the ED, because, well, it doesn't usually matter to us whether the rhythm is caused by intranodal reentry (as in AV nodal reentrant tachycardia, or AVNRT) or extranodal reentry (as in AV reentrant tachycardia, or AVRT). This family of arrhythmias is almost always safe, even if the ECG shows ST depression, or we find a small troponin bump after conversion.

But the differentiation between different types of PSVTs is very important to the cardiologist, as there are implications for therapy. For example, AVRT is almost always primarily treated with an ablation. AVNRT, however, often is first treated a trial of medications (such as calcium-channel blockers, beta-blockers, or even digoxin), although ablation remains an option. 

So when one of the new cardiologists, Ram Gordon, from Cardiac Specialists, pointed out some interesting features on Mrs Black's ECG, we took the opportunity to expand our ECG skill set.


True fact: He's an ER fan!
Thanks to this brief, "just-in-time" teaching in the ED, when Mr. White was brought into the ER (just 2 hours after Mrs Black!), we were primed. Yuko & I only had to look at the ECG, and then at each other - we  had the diagnosis already.

Analyzing the initial ECGs
There's a good bit of cardiology literature devoted to making this diagnosis (AVRT vs AVNRT) using just the surface ECG. 

(If you want to do your own "deep dive" in this area, start of with these three articles, for example: Combined evaluation of bedside clinical variables and the electrocardiogram...Electrocardiographic differential diagnosis of narrow QRS complex tachycardia, and EGC diagnosis of paroxysmal supraventricular tachycardias...,.)

If, however, you don't feel like tackling the primary literature, you can instead check out this table, summarizing the elements that distinguish AVNRT form AVRT on the ECG:


Source: Gonzalez-Torrecilla 2011
Let's go use this information to evaluate the ECGs from Mr White and Mrs Black!

First let's look at Mrs Black's ECG. Are there indications of atrial activity? The best leads for this are usually II and V1. Typically the P-wave is upright in II, and inverted in V1, but a close look at those leads...
Detail of "Mrs Black - before"
... reveals inverted P's in II, falling just after the QRS complex - I'll say about 100 ms afterwards. It's also hard to ignore the ST depression in II and aVF!

These elements all suggest that this is an orthodromic AVRT, using a concealed pathway. Looks like the electrophysiologist has to go looking for a bypass tract!

Ok, what about Mr White?

You remember Mr White? He has a cool-sounding name.
A close look at Mr White's ECG shows...


Detail of "Mr White - Before"
... inverted P waves in II and III, with a suggestion of an upright P wave imposed on the T wave. Also, the RP interval is about 100 ms, and is distinct from the QRS complex. As long as that inverted P wave is distinct, and not "slurred" into a sort of "pseudo S' wave," it points to AVRT.

Pseudo S' in AVNRT, before & after conversion.   Source

So what?
So what's the big deal? Diagnosing an AVRT versus AVNRT in the ED isn't really crucial to the immediate management. So why should you try and delve deeper into the ECG? 

Well, first off, in EM we have the tough job of trying to sound smart to a lot of specialists (without ending up sounding too clever by half!). In any one shift, you'll find yourself describing an "overlapping distal radial fracture with intraarticular extension" to an orthopedist, a "perilimbal flush with consensual photophobia" to an ophthalmologist, and "He says he wants detox. Again." to the social worker. Similarly, in cardiology, we should using the language of their field, describing inverted Ps, pseudo S' waves, and such.

Furthermore, we can help point the patient in the right direction sooner. Evidence of AVRT, for example, suggests that we should talk with an electrophysiologist before discharge, arranging follow-up.


Lastly, you can't know too much about ECGs. Emergency physicians have to be experts in acute cardiology, give the pivotal role we have in the system. We can't afford to be second-best to anyone in the hospital, especially at 0300!

Thanks again to Dr Gordon for inspiring this post, and assisting with the cardiology perspective!

Wednesday, November 28, 2012

How to cure incomplete RBBB.

I had an interesting sign-out yesterday. The patient was a 30-ish year old woman with some vague complaint that localized to somewhere between her eyes and her knees. The off-going physician is a model of thoroughness, and they mentioned that the patient was getting, amongst other tests, a CT for pulmonary embolism.

"I wasn't really thinking PE at first," they explained to me, "but after I saw the incomplete RBBB on the ECG, I sent a D-dimer." The D-dimer, of course, came back trivially elevated, and the CT had been ordered.

Ah, the scourge of the IRBBB. It typically take the appearance of an rSR' pattern in V1 and V2 with a narrow QRS, although the AHA takes a dim view of this colloquial definition.

This seemingly "hard" element of evidence, however, can be surprisingly malleable!

I cured the patient's IRBBB!
The patient was already off at CT, so I looked at the ECG myself. It looked pretty darn normal, except for the right-precordial leads:


V2 shows an rSR' pattern, clearly.

The patient returned from CT scan, and I awaited the results. In the meantime, however, I re-interviewed an examined the patient, and convinced myself that she was low risk for all of the "bad actors." The IRBBB stuck in my craw, however, and after some fiddling around, I aquired a new ECG.

Sweet. It's not up there with sinking a difficult tube, or threading a pacer wire, but it makes for a cleaner chart!

What did I do?
I put V1 and V2 where they are supposed to go.

For a fuller explanation of the background here, please check out The most difficult step in obtaining an ECG. It's a post I wrote for paramedics about the importance, as well as the common difficulty, of placing the precordial leads in the correct locations. It's written in a conversational and witty tone, with plenty of illustrations - you'll like it!

Suffice it to say, though, that V1 and V2 are usually placed far too high on the chest. This produces a number of artifacts, including pseudo-infarction patterns and, yes, IRBBB.

I took a picture (with the patient's knowledge and permission - she believes in education!) of the actual lead placements on the patient's chest. The electrode wires are attached to the proper locations, at the 4th intercostal spaces, just to the right and left of the sternum.

Thank you Ms Anonymous!
The other electrode stickers are located only about 5-7 cm higher, around the 2nd or 3rd intercostal spaces, but it was enough to produce the spurious IRBBB.

The Bottom Line
Learn where to put the leads yourself.

If the diagnosis is going to rely critically on the ECG, you ought to check out where the electrodes were placed by the nurse, tech, or paramedic. Certainly, if there are abnormalities isolated to the precordial leads you should go back and do this, especially if the ECG doesn't match the patient's age or presentation.

BONUS QUESTION: For major extra points at the "Port, tell me what electrophysiologic diagnosis may rely on placing V1 and V2 higher than usual.

(Answer can be found by checking my self-aggrandizing link.)

*******
Added post-publication.

Mr Várhegyi points out a similar example, elsewhere on the web, of an IRBBB. Oddly, that example seemed to show some QRS prolongation in V2 that was not appreciated in the other leads.

Source

So, I took another look at my patient's initial ECG:


Darned if it doesn't seem to also have an isolated, minor (< 0.02 seconds), QRS prolongation in V2.

I'm going to defer providing an explanation until I have some idea about why this occurs, or even declaring that this is a reliable feature of improperly placed precordial leads. But it's apparent in these two examples. I'll look into it - anyone else with a better idea write in!


Monday, November 19, 2012

"Mystery" bradycardia, with some irony

Kito and I had an interesting patient last month. 

The patient
I had just been teaching a paramedic student some fine points of the ECG, when nurses asked us to come to room 41.

A 70 y.o. woman was brought in by EMS. She had syncoped when she stood up from the toilet. No zebras there - happens all the time! Her past medical history was about fair for her age; DM2, HTN, CAD, hyperlipidemia, etc, and on Plavix but no warfarin. She had gotten pretty banged up, with injuries to her face and leg.

What really stood out was that her heart rate; around 40. Her blood pressure was stable at 101/66, though, and she denied any chest pressure or trouble breathing.

The ECGs
Her first ECG was obtained at 18:24



A quick check of an old ECG (1 year prior) revealed that the LBBB, at least, was old:



Huh.

The Assessment
A review of her medications from her last ED visit listed carvedilol, and so accidental supratherapeutic dosing seemed likely. Line, labs, and imaging of her injuries were ordered, and we kept a close eye on the monitor.  Her blood pressure stayed north of 100, so we held off on pacers and pressors. Once she was cleared of any traumatic issues, she would be an easy CCU admit. Done.

Ah, not so fast...







 The Denouement

"This is the lab, and we have a critical value to report."

I actually like these phone calls - It's like a Maury Povich-type moment. You know that in the next few moments, all the pieces will fall into place, and you'll either be dancing around in self-congratulation, or applying both palms to your face firmly, rocking back and forth.


It wasn't the troponin, as I had been suspecting.

Instead, it was the potassium that turned up high - a level of 6.6 in fact. For some reason our patient, who had mild CKD before, now had a BUN of 104, and a GFR of 24.

Interestingly, renal and cardiology were not very impressed by the potassium level, feeling that it was a bit low to really cause much trouble. Kito & I had already started treatment, however. After 3 grams of calcium gluconate, the heart rate picked up, and we grabbed another ECG (21:17).


Seemed like we were on the right path, so we started dextrose and insulin, hung normal saline to address the AKI, and eventually gave some Kayexalate (Yes, I know what Weingart said on EmCrit, but a lot of folks still expect you to give it).

The Point

It's not just about tented T-waves.

I'm not going to review all of the protean ways that this electrolyte problem can manifest (please check out the comprehensive article by Matu et al).  I just want to emphasize how it showed up here.

First, there was an unexplained bradycardia, along with PR prolongation. Lastly, there was ST-segment depression in the anterior leads. In retrospect, these were classic signs of hyperkalemia, with plenty of examples from the literature.

Two cases, for example, describes complete AV block, but with a narrow QRS complex. Other cases demonstrate severe bradycardias without tented T-waves or pronounced QRS widening; e.g.

Case 1 from Atropine-resitant bradycardia due to hyperkalemia
You can even see some Wenkebach action, again without the dramatic T- or QRS-wave;

Wenckebach Block due to Hyperkalemia

You get the idea - you can go Google more examples if you want!

And the irony mentioned in the title?
As I mentioned above, I had been teaching ECG stuff to a medic student before this patient came in.  I could have been speaking with her about any number of topics - STEMIs, treating VT, recognizing atrial flutter... But no. 

Of course, it was about recognition of hyperkalemia on the ECG!