Category Archives: Electrophysiology

Hacking the QTc

Long QT, torsade de pointes

The QT interval—a measure of the duration of the overlapping action potentials from two billion ventricular muscle cells—has fascinated physiologists since the dawn of electocardiography.  Too long or too short, it can be a harbinger of ventricular arrhythmias and sudden death. Sensitive to electrolytes, drugs, and autonomic tone, susceptible to congenital ionic channel mutations, difficult to measure (which lead? where does it end? what about the U wave?), and markedly varying with heart rate—the QT interval is clinically important and, at the same time, elusive.  To distill the essence of the QT interval and separate out the volatile heart rate dependent components,  the corrected QT interval (QTc) was devised.   Succumbing like everything else to automation, the QTc has become just another number printed in the upper left corner of a digital electrocardiogram, along with the PR and QRS intervals, the QRS axis, and the patient ID. Lulled into complacency by its automatic generation via algorithm (despite the lurking disquiet engendered by the knowledge that the very same algorithm occasionally reads normal sinus rhythm during complete heart block), few bother to ask: Where does that number come from? What formula was used to derive it?  Is the corrected interval actually correct?

For those who care about such questions, the QT can be manually measured and the QTc calculated. Most use the hoary Bazett formula dating from 1920, relating the QT to the square root of the cardiac cycle length. Some are aware of a few other formulas: Fridericia, Hodges, or Framingham. There are many online and native app QTc calculators–in fact my apps EP Mobile and EP Calipers have built-in calculators for all four formulas. There seems to be little need for yet another QTc calculator app.  Nevertheless I have written one, EP QTc, and I should explain how that came about.

Formulas, formulæ

There are more QT corrective or predictive formulas in the medical literature than you might imagine—at least 40.   Rabkin et al. collected 31 of these formulas and worked out a standard nomenclature and classification scheme. Rabkin does not actually give the mathematical equations involved. In fact, nowhere are these formulas collected in a single source.  And what good are formulas if you can’t apply them?  On a whim I thought it would be interesting to write an app that would calculate the QTc using not just one or four formulas, but all the formulas given by Rabkin. The app would also provide details about each formula and statistics and graphs of the results.  I wasn’t sure who would be interested in such an app (probably no one), but at the same time I saw it as a simple project that might make QTc calculating more fun while putting this mass of QT correction literature into perspective. It turns out, it wasn’t such an easy matter.

Paywalls galore

Starting at the beginning, I looked up Bazett’s original article published in 1920. The only online source for the Bazett article is the Wiley Online library.  The site says the article was first published on October 27,  2006.  No, the article is from 1920, and this is a reprint of the original.   According to US copyright law, anything published before 1923 is in the public domain. I’m sorry, but reprinting an article that is in the public domain does not restart the copyright clock.  Nevertheless, the only way to get a digital copy of this historically important article is to pay an extortion fee of $38 to the wily racketeers at Wiley who have managed to kidnap this article and hold it hostage for almost a century.

What was true of Bazett was also true of the vast majority of the articles I was seeking.  The QT correction literature like most science is locked up behind paywalls.  Lacking institutional access and repelled by the idea of shelling out vast quantities of cash for papers many of which were in the public domain, I faced a major obstacle. Fortunately I enlisted some colleagues with digital library access to help liberate these publications, and I eventually managed to get nearly all the primary sources for the different QT formulas.  Beyond these paywalls, there were other lesser hurtles to leap over, but we’ll get to them later.  In the meantime, you may be asking…

What’s wrong with Bazett?

Most every QTc calculator uses the Bazett formula. Why not? It’s simple and can be solved with any device (slide rule or something more advanced perhaps) that does square roots. It was the first QTc formula developed. So why were 30 or more other investigators dissatisfied with Bazett and felt the need to develop their own formulas? What’s wrong with classic Bazett?

Reading the original Bazett article is interesting (though still not worth $38). We travel back to a simpler time when the ECG was relatively new, and the only leads were I, II, and III.  Bazett was interested in the dependence of the duration of mechanical systole on heart rate, and, lo, this particular interval on the ECG, the QT, seemed like a good surrogate to study this. Professor Bazett was able to gather a grand total of 39 healthy subjects, 20 men and 19 women, aged 14 to 53 (though one subject’s age is listed merely as “Boy”) and measure their heart rates and QT intervals.  In some cases individual values were given, in others averages of several values were used. Several  subjects were not his own, but data borrowed from Dr. Thomas Lewis. From this small selection of messy data points Bazett came up with what is still considered the gold standard QTc formula used today:

QTc = QT/√RR.

QTc or QTp?

Well, not exactly. Bazett and most of the early investigators did not create QTc formulas, i.e. formulas intended to give an idealized QT interval independent of heart rate. Bazett and his colleagues were interested in predicting what the QT interval should be at different heart rates. This is the QTp, the predicted QT interval.1 Bazett’s published formula was:

QT = K √RR where K = 0.37 for men and 0.40 for women with units in secs

Similarly the Fridericia formula, also published in 1920 was:

QT = 8.22 ∛RR with units in 0.01 sec

Yes, you read that right. The units are hundreds of seconds. Ugh.

As it turns out one can mathematically convert any QTp formula to a QTc formula, given the assumption that the QTc is independent of heart rate and the QTc equals the QTp at a heart rate of 60. The process is left as an exercise for the reader :).  Later authors took the Bazett, Friedericia and many other QTp formulas and converted them to clinically more useful QTc formulas.

In search of a better Bazett

No one was able to reproduce Bazett’s results. Many authors found that Bazett’s QTc formula tended to overcorrect the measured QT interval at high heart rates, and undercorrect it at low heart rates (e.g. see here). Certainly with such a low N and primitive methodology, Bazett may have mischaracterized the QT vs RR curve. Perhaps the exponent in the formula is not 0.5, or perhaps relating the QT to a power of the RR is not even the right kind of function to use.  The disturbing fact is that each group of investigators who has studied the relationship between the QT interval and heart rate has come up with a different formula.

Linear, power, logarithmic, exponential—oh my!

In reviewing the QT papers, including some studies using 10s of thousands of patients, it is remarkable how inconsistent the findings are with regard to the shape of the QT vs RR curve. Some authors find a straight line, with a linear function underpinning the relationship. Others find curvature at either end of the heart rate spectrum.  The resultant equations are sometimes logarithmic or exponential.

Rabkin uses a classification that I used in the EP QTc app.

ClassificationQTpQTc
linearQT = b + a*RR QTc = QT + a(1-RR)
rationalQT = b + a/RR QTc = QT + a(1/RR - 1)
powerQT = b RR^aQTc = QT/RR^a
logarithmicQT = b + a*ln(RR) QTc = QT - a*ln(RR)
exponentialQT = b + a*e^-RR QTc = QT + a*(e^-RR - 1/e)

(* = multiplication, ^ = raised to the power.  Table modified from Malik et al.)

This table also shows how each QTp formula can be converted to a QTc formula. Any QTp formula can be converted to a QTc formula, so theoretically there are as many QTc formulas as QTp formulas.  Rabkin lists many more QTp formulas than QTc formulas.  Evidently in many cases the conversion has not been considered worth the effort to do.

Typos and unit confusion

Back to the vicissitudes of creating the EP QTc app.  The tale of woe continues with multitudes of typographical errors in the sources and inconsistency of units in the formulas. Typos include mistranscribing formulas in secondary sources (e.g. reading 7 instead of 1 in a tiny exponent), rounding errors, and just plain poor proofreading. I will not mention specific sources, but these types of mistakes seem to be common in the medical literature.  Sure glad we’re paying those publishers all that money for quality control.

As to unit confusion, we already alluded to the use of 0.01 sec as the base unit in the Fridericia formula. Various authors use heart rate as opposed to cycle length in their formulas.  They are inversely related and the use of different terms makes it hard to compare formulas to each other.   Adding to the confusion is that formulas almost invariably use an RR interval measured in seconds, but then sometimes in the same formula require a QT in milliseconds.   Sometimes the units used for the dependent variables aren’t made clear.   Most authors also don’t seem to realize that the results of non-linear QTc formulas aren’t really in units of sec or msec. For example, Bazett QTc units are sec/√sec, i.e. √sec (or worse, msec/√sec).  To be fair, I sidestep this issue in the EP QTc app as well.  To my mind this unit confusion just emphasizes what an artificial thing a QTc is.

Nomenclature

Having obtained sources for all the formulas mentioned in Rabkin (and a few more), I applied Rabkin’s proposed nomenclature. This consists of a 6 letter code for each formula: the first 3 letters QTc or QTp, and the last three based on the first author’s last name. Thus Bazett’s QTc formula is QTcBZT. The Framingham study QTc formula, less well known by its first author (Sagie) is QTcFRM. There are some inconsistencies in the nomenclature which I have tried to correct. For example, Kligfield’s formula is given as QTpKLN in Rabkin, since Kligfield is misspelled as Klingfield. Oh well.

Sex and age

Some formulas differ depending on the sex or age of the subject, or both. The QT interval tends to increase with age and is longer in adult women. So some formulas require entering the age and/or sex. These formulas will simply refuse to give a result if these parameters aren’t present.

A tough question is how to apply QT formulas to subjects that don’t match the study population. I excluded formulas that were derived only from children. All of the study populations are predominantly based on adults, but in a few children were also included. Some studies used men only as subjects.  Is it reasonable to apply a formula derived from data from only men to a woman? In the EP QTc app I avoid such issues and leave it up to the user to deal with this question.

What is normal?

Here is another Pandora’s Box. Just as there are many QTc formulas, there are many papers dealing with establishing the normal QTc. Given syndromes of sudden death related to short QT intervals, both boundaries of normal need to be considered. I have gathered these papers together along with their QT interval cutoffs. These are often sex-specific, and sometimes gradations of abnormality are assigned, e.g. borderline and abnormal, or mildly, moderately, or severely prolonged. In the app the user can select from among these published criteria to define whether a result is normal or not.  In practical clinical use, the QTc interval is only one component in the risk scales needed to establish the diagnosis of long or short QT syndrome.

What about QTp intervals?

By definition a QTp interval is normal. Rabkin proposes that, since QTp formulas were derived from multiple different populations, QT intervals outside the range of all defined QTp intervals may be considered abnormal. I have implemented this algorithm in the EP QTc app. One objection to this approach is that QTp formulas (with some exceptions) give mean values for normal QT intervals.  Thus one would expect the range of normal QT intervals to be somewhat larger than the range of all possible QTp intervals. One should probably take this into account when interpreting the QT vs QTp interval statistics and graphs.

QT library and EP QTc app

All of the data on QTc and QTp formulas have been incorporated into a QTc library. This library is open source and free to use. It can be used with any iOS or macOS project. The library includes functions that make it easy to calculate the QTc or QTp by any formula, using any input (RR or heart rate, sec or msec). In addition information such as references and DOI links, notes, equations, and study populations can be easily assessed. For technical use of the QTc library see the README.

The EP QTc app was originally intended just as a demo app for the QTc library, but it has numerous features making it useful in its own right. Use it to calculate the QTc and QTp using 33 formulas. Graph and do statistics on the results. Copy the results to spreadsheet programs. Options to change precision, sort the results, use different QTc cutoffs from the literature and others are all available.  The source code is on GitHub, and I hope the app will soon be on the Apple App Store.

Finale

I’m not sure who will use the EP QTc app. Maybe no one. It is certainly overkill. If you just want an occasional Bazett QTc it may not be worth it. If you want to explore this minor corner of the literature further, it may interest you. At worst, you can at least impress your friends when you tell them the QTpMRR for your patient.

Some screenshots

Main calculator screen
QTc graph
Statistics screen
QTc results screen
Details screen
QTc limits screen
QT, QTp vs heart rate
Preferences screen
QTp graph

The End of Cardiostim

A few days ago I received an announcement by email that the Cardiostim meeting for 2018 has been cancelled. The Cardiostim website confirms this, and it looks like the meeting is gone for good.

Back in June, 2000, while still an academic electrophysiologist at the University of Colorado, I attended my first Cardiostim meeting in Nice, France. I loved it. The beautiful weather, the azure Mediterranean, the restaurants and cafés, and the charm of “Old Nice” were a relaxing break from work. The abstract presentations, poster sessions, and workshops were not too different from those of the Heart Rhythm Society back home, though obviously the European influence was greater. For good or ill, the lack of an FDA meant the Europeans got to play with new technology sooner than we did. Sure, industry was there in a large hall with all their exhibits, just like at HRS. But when they realized I was an American they didn’t really bother me. Their targets were the Europeans.

An electrophysiologist in Nice

The coffee, bread, and pastries were excellent.

Two years later, I brought a couple of my fellows with me back to Cardiostim. They presented a poster and a couple of abstracts. I went swimming out to the buoys off-shore. I ran a 5K sponsored by Biosense-Webster along the Promenade des Anglais. It was a great experience for the fellows and another enjoyable visit for me.

In 2003 I went into private practice with a large cardiology group in Kentucky. Nevertheless in 2004, and every two years after that (the meeting was biannual), I attended Cardiostim. Along the way I dumped HRS, tired of the conflict of interest between its mission to represent electrophysiologists and its industry support, whose goal was to expand device implantation by recruiting non-electrophysiologists to implant. And so Cardiostim became a biannual bright spot to look forward to during the drudgery of private practice.

The last Cardiostim I attended was in 2012. In 2014 I returned to Nice during Cardiostim, but I didn’t attend the meetings. I had retired from medicine. Nevertheless it was fun to see the city invaded one more time by the nerdy guys in their blue blazers (and women in equivalent uniforms) carrying their Cardiostim bags. It was clear the electrophysiologists were in town.

Cardiostim swag

In 2016 I didn’t visit during Cardiostim.   Later that year, in November,  I was in Villefranche-sur-mer, the town next door, at the Institut Français, pursuing my post-retirement goal of learning French. The Institut had fewer than their usual number of students that year. Enrollment had dropped after the terrorist truck attack in Nice on Bastille Day. That had occurred after Cardiostim. We visited Nice. Hundreds of hand-made memorials had been placed in a park adjacent to the Promenade des Anglais. The Promenade itself was in disarray. Areas of fencing and pavement were being repaired. New pylons were being put up, as an after-the-fact defence against a sickness that can’t be cured by putting up pylons. Nevertheless people were stretched out on the rocky beach as usual, joggers and cyclists plied the pavement, and business carried on as usual.  Although this attack had nothing to do with the end of Cardiostim (which was apparently due to Europace splitting off from them and lack of industry support), it seems like a sad coincidence that the meeting died after that vile attack.

So, goodbye Cardiostim.  Thanks for the memories.

Informal memorial to the Bastille Day victims
Nice on the Côte d’Azur
Cardiostim

George Mines and the Impermanence of Knowledge

George Mines

It was a chilly Fall morning in Montreal. A Saturday, the campus of McGill University was quiet. Students, not much different in 1914 from those of today, were sleeping off their Friday night activities. A cleaning woman entered the Physiology Laboratory to dust the glassware and wash the floors. As she turned a corner she was startled to see a young dark-haired man, sitting in a chair. She recognized Professor Mines, the handsome English scientist whom she had often seen working in the laboratory at odd hours. He appeared to be sleeping. His shirt was open and a strange apparatus was strapped to his chest. Rubber tubing stretched from this apparatus to a table filled with equipment next to him. A smoked paper drum rotated slowly. The needle of the drum was motionless, then suddenly jumped. Startled, she let out a little gasp. “Professor, Professor,” she called out. “Are you alright?” She noted he looked very pale, deathly so. She touched his hand. It was cold.

She ran to get help. The police took Professor George Mines to the hospital. There he briefly regained consciousness, but not long enough for him to explain what had happened. He died later that day. He was 29 years old. During his brief life, he used animal models to describe the physiology of reentry in the heart. He described the mechanism of supraventricular tachycardia in Wolff-Parkinson-White Syndrome long before that syndrome was described. He used a telegraph key to deliver timed electrical shocks to rabbit hearts, inducing ventricular fibrillation which he described without the benefit of an electrocardiogram. He thus was the first to report the existence of the ventricular vulnerable period. Despite all this amazing work, much of what he discovered was little noted at the time, until “rediscovered” by later researchers.

It seems likely that he was the first to induce arrhythmias in a human, long before the field of clinical cardiac electrophysiology. Unfortunately that human was himself, and the result was his own death.

The published papers of George Mines are fascinating to read. His very primitive equipment by today’s standards was more than compensated for by his remarkable ingenuity and keen powers of observation and reasoning.  He described the relationships between conduction velocity and refractoriness in reentry, the existence of an excitable gap, and deduced the reentrant nature of ventricular fibrillation. In one memorable experiment he cut fibrillating tissue into larger and larger loops until he was left with just one circulating wavefront. Amazing stuff! What more would he have accomplished had his life not been cut short?

Back in the days before the Internet, I used to keep photocopies of medical articles in a file cabinet (actually several large file cabinets). In those days of academia I enjoyed going to the stacks of the medical library and randomly reading articles from old bound journals, some dating back to the 19th century.  I learned a lot.  One thing I learned was that science has a problem with collective amnesia.  Discoveries are often forgotten or ignored, only to be rediscovered years later.

Nowadays everything is online. Or is it? Recently I wanted to look up Bazett’s original article on correcting the QT interval for heart rate. It was published in Heart in 1920 (Bazett HC. (1920). “An analysis of the time-relations of electrocardiograms”. Heart (7): 353–370.) These old volumes of Heart have not been digitized and are not online. Such a famous article though is surely reprinted? Indeed it is, on the Wiley Online Library site. I can get a copy of the PDF for $38. Absurd! An article from 1920 costs $38!

Here we see the bitrot of science, the impermanence of knowledge. On the one hand, modern scientific research is largely hidden behind a paywall, so that the poor (in the financial sense) reader must rely on abstracts, news reports, online sites such as Medscape, and presentations at medical meetings to keep up-to-date, instead of a careful reading of research methods and results. On the other hand, our precious scientific heritage, the published papers of previous generations, remains largely undigitized, residing in the dusty stacks of libraries, increasingly ignored by newer generations to whom nothing matters if it is not online. There are some exceptions. The Journal of Physiology has digitized all of its content back to Volume 1 from 1878. But most publishers haven’t bothered doing this.

At least half of early films have been lost. Early TV archives, like those of Dr. Who were routinely destroyed or copied over, resulting in loss of these shows forever. The situation is not so dire with old scientific research. The libraries will remain for a long time, and paper has a good half-life. But the beautiful work of George Mines and those like him, the true pioneers of medicine, will remain largely obscure to future generations unless that work is available online.

Perhaps some portion of the $38 for a PDF copy of a 1920 article could go to that cause.

EP Studios App Updates

Here’s what’s going on with the EP Studios apps:

EP Calipers

Most of the new stuff is in EP Calipers. Probably the most useful new feature is available on the Mac and Windows versions: a transparent floating caliper window. Use it to overlay calipers over any open window on the desktop. Check figures of journal articles. Use it during slide shows. Use it on webpages or on your EHR. No longer are you limited to just image files you have downloaded onto your computer. Unfortunately due to the nature of mobile device platforms, there is no way to implement similar functionality on a phone or tablet (that I know of).

Using the floating transparent window to check measurements in a published academic paper. It appears the pacing CL is actually 240, not 250 msec.

Several users suggested the capability to color each caliper differently. This is now implemented. Others wanted a way to fine tune caliper position besides just dragging with your finger or trackpad/mouse. This is also implemented, via keyboard arrow keys or buttons that “micromove” or “tweak” caliper positioning.

Finally, in case you missed it, angle calipers are available. They can be useful in Brugada syndrome, in which the so-called beta angle may have predictive value. In addition, the work of Dr. Adrian Baranchuk from Queen’s University in Kingston, Ontario indicates that there is prognostic value to measuring the base of the triangle formed by the angle 5 mm inferior to the beta angle triangle’s apex. EP Calipers now supports this. Provided amplitude has been calibrated in mm, the triangle base is automatically drawn showing this measurement. This technique has been dubbed by Dr. Baranchuk as a “Brugadometer.”  More information on these Brugada Syndrome ECG measurements can be found here.

Using the Brugadometer to measure the beta angle and the triangle base 5 mm below the apex.

EP Coding

EP Coding also received a major update earlier this year. After a few years of relative stasis, the AMA decided to shake up the coding of EP procedures once again by unbundling the sedation component from the procedure codes. The result is a relatively complex coding system for sedation, depending on factors of patient age, who does the sedation, and the sedation duration. EP Coding now allows you to calculate the sedation codes automatically using a sedation coding calculator.

Sedation coding calculator

 

EP Mobile

EP Mobile has been relatively static. It is already chock full of calculators, drug information, risk scores, pictures of ECGs, etc. It is our best selling app, so we must be doing something right. I am always happy to add features; just email me at mannd@epstudiossoftware.com with your requests.

Final thoughts

This is a bit off-topic, but probably not worth a separate blog post either. My old Motorola Droid Maxx Android phone is getting a bit long in the tooth, and way past upgrade time. I was an early adapter of Android, and though I use other Apple products (a Macbook Pro and an iPad Mini 2), I have never owned an iPhone. This may change. In many ways I think Android is a more innovative operating system than Apple’s iOS. Nevertheless we live in an insecure world, and I can’t get timely updates to Android via my phone and Verizon. My phone is stuck on Android 4.4.4 (I even forget what candy that is), whereas the most recent Android version is Android 7 Nougat.  Apple doesn’t have this problem.  Having an outdated, obsolete OS in the current world of bad guy hackers is untenable. I think the problem is (as usual) with the providers, who could care less about updating an older phone when they could be pushing the latest phones on customers. The 2 year cycle of upgrading phones is ridiculously wasteful. But that’s what is driving the industry, with the carriers all too eager to get you in and sign another rip-off contract. So, it might be goodbye to Android soon.

Thoughts on Mark Josephson

I’m sure there will be plenty of tributes to Dr. Josephson in the next few days from his colleagues who knew him well and those who didn’t know him personally but learned so much from his books and articles. I fall somewhere in the middle. I wasn’t one of his students at Penn who learned from him directly. I did meet him several times. I did work for years at the University of Colorado with Alden Harken, the surgeon with whom Dr. Josephson developed the “Pennsylvania Peel” — endocardial resection, the first surgical treatment for ventricular tachycardia. Oh, and I did live in the same apartment Mark used to live in during my cardiology fellowship in Philadelphia in the 1970s. More on that later.

Mark Josephson may represent somewhat of a dying breed in academia. In the great academic triad of clinical care, research, and teaching, the last element, teaching, which makes the least money for institutions, is emphasized less and less. Dr. Josephson excelled as a teacher. A lucky few were able to experience his teaching skills first-hand. A far greater number learned from his writing, in particular, from his opus magnum Clinical Cardiac Electrophysiology. Originally a relatively small but densely written book in a red binding, subsequent editions were more massive, filled with page after page of painstakingly labeled intracardiac recordings and clear-cut explanations of obscure electrophysiologic phenomena. I cut my teeth on this book, reading the original through when I was an EP fellow in Houston, and then reading the 2nd edition straight through when preparing for my first EP boards.

The book was important because it set a standard for analysis of intracardiac recordings that inspired subsequent researchers and students of the field. Back in the 70s and 80s, the mechanisms for most major arrhythmias (with the exception perhaps of atrial fibrillation) were worked out solely by analysis of intracardiac recordings and a few pacing techniques. Mark Josephson was instrumental in this process. Back then, working on arrhythmia mechanisms was the important thing. Therapies for ventricular tachycardia were drugs like quinidine or procainamide, and EP-guided drug therapy was, in retrospective, a pseudoscience. Yet working out the mechanisms of WPW syndrome, supraventricular tachycardia, and ventricular tachycardia eventually led to effective ablation and device therapy in the 1990s and beyond.

Dr. Josephson, who along with a cadre of first-generation EP superstars trained by Dr. Anthony Damato (the “godfather” of EP) at the Staten Island Public Health Hospital, set a standard for teaching in the field of electrophysiology that was often emulated, but never matched. Moreover he wrote a number of incisive editorials over the years in an attempt to keep the field rooted in its scientific basis, rather than be swept away by the insidious influence of industry or the idea that it wasn’t necessary to understand the pathophysiology of an arrhythmia if you were just going to burn it away.

As mentioned above, I was lucky enough to meet him on a few occasions and to round with him. By coincidence we discovered that the apartment on Henry Avenue in Philadelphia where I lived when I was a fellow was the exact same apartment he had lived in several years before. He remembered well the old guy who lived one floor above us, a fellow by the name of Sullivan, nicknamed “Sully.” I was just a plain cardiology fellow when I lived there, only subsequently deciding to go into EP and move to Houston for training. I always wondered if I picked up some kind of EP karma from living there. Who knows?

The advances in diagnosis and treatment of arrhythmias that have occurred since the 1970s are extraordinary, and uncounted numbers of people have benefited from these advances.  It seems a shame that most lay people, saddened at the loss of actors, musicians, sports heroes, and other celebrities, have no knowledge whatsoever of the passing of people who have actually had much more impact on their lives, like Dr. Josephson.  So it’s up to us, his colleagues, to remember Mark Josephson and give thanks for his incredible contributions to medicine and the world.

Massive Heart Attacks

Google Ngram of the phrase “massive heart attack”

Carrie Fisher’s sad, premature death is an occasion to reflect upon the poor job the news media does in reporting medical news. The initial report from TMZ had the headline “Carrie Fisher Massive Heart Attack on Plane.” If one equates “heart attack” to the more precise medical term “myocardial infarction,” as is usually done, then this is certainly diagnostic overreach on the part of TMZ. From their report it appears that Fisher suffered a cardiac arrest; indeed that term is used in the body of the article. So why not use that term in their headline? Perhaps massive heart attack sounds more dramatic. The word “massive” seems to go naturally with “heart attack.” Try to think of other phrases in which massive fits so well. Massive hack? Massive debt, perhaps? Few phrases roll off the tongue as well as “massive heart attack.” But most of the time when used by the media this phrase is not at all accurate.  Rather it is a catch-all term to indicate something serious related to the heart has occurred.

Of course we don’t know exactly what happened to Carrie Fisher, nor is it any of our business, but none of the information available indicates that she had a large myocardial infarction as opposed to a primary arrhythmic event like ventricular fibrillation or ventricular tachycardia. As a cardiologist having seen this sort of event a depressingly large number of times it is possible to speculate on what happened.  She likely suffered a cardiac arrest related to an abnormal heart rhythm starting suddenly in the heart’s ventricles.  Lay persons and the media often refer to this as the heart “stopping.”  While the pumping of the heart stops or is reduced, in actuality the heart is beating very fast or in a disorganized fashion to the point where it can’t effectively pump blood.   Without rapid correction using an electrical defibrillator this leads to sudden death.

In Carrie Fisher’s case CPR was administered while the plane was still in flight. It is unclear how much time elapsed between the onset of the cardiac arrest and administration of CPR.  It is difficult to tell from the reports if an AED was used on the plane or if defibrillation was attempted only after the plane landed.   We know she never regained consciousness and most likely suffered brain death due to prolonged interrupted circulation.

Carrie Fisher was a cigarette smoker and used cocaine, at least during her Star Wars days.  Could heart disease caused by smoking and drug use have contributed to her sudden death? Could more recent use of drugs like cocaine have been a factor? We don’t know, but if the family deems it fitting that the circumstances of her death be made public, it might help educate the public and the news media on some of the nuances of heart disease and the difference between a “massive heart attack” and a cardiac arrest.

Finally it is interesting to examine some of this lay cardiac terminology using Google Ngrams. The Google Ngram site is a search engine that can be used to look up the frequency of words or phrases in thousands of books published over many years. It can help establish when certain phrases like “heart attack” or “cardiac arrest” were first used and when they became popular. The Ngram at the top of this post of the phrase “massive heart attack” shows the rise in popularity of this phrase over the last 50 years. The Ngram below compares the terms “heart attack”, “myocardial infarction”, “sudden death”, and “cardiac arrest.” It is interesting that “sudden death” is a term that has been used without much change in frequency since the year 1800. “Myocardial infarction” and “cardiac arrest” both entered the literature around 1930-1940. “Heart attack” dates back to around 1920, but has become more and more popular, while the medical term, “myocardial infarction” seems to be less used recently. Curiously although the phrase “heart attack” has been around since the 1920s, it is only since 1960 that the phrase “massive heart attack” has become popular.  One wonders why.  These kinds of results are open to all kinds of interpretation: I’ll leave that to the reader as an exercise. But I encourage you to try Ngrams out yourself, on any subject that interests you. The results are often fascinating.

Google Ngram of other heart attack related phrases

EP Calipers for Windows

EP Calipers for Windows
EP Calipers for Windows

EP Calipers for Windows is done.  Whew.  As stated in my previous post, porting the app to Windows was a bit of a struggle.  Installing tools like a bash shell, git and Emacs took some time and effort.  The Windows tool to bridge iOS apps didn’t work.  So I was forced to port the code from objective C to C# and .NET by hand.  This took some time.

Looking back on my previous post with the benefit of hindsight, I think I was a bit too harsh on the Windows development environment.  I grew fond of C#, the .NET API, and the Visual Studio IDE as I got used to them.  Visual Studio is at least as good, if not better, than Xcode, Eclipse, or Android Studio.  Kudos to the Microsoft developers.

EP Calipers is a Windows forms app, meaning it runs on desktop, laptop, and tablet versions of Windows 10.  It is not a Universal Windows Platform (UWP) app.  With the market share of Windows phones dropping below 1%, and doubting that anyone would run EP Calipers on an X-box, I didn’t see any point in developing a UWP app.  I know most hospital desktops run Windows (though how many run Windows 10 now, I wonder?), and many docs have Windows laptops or tablets.  An app targeting the traditional Windows desktop seemed like the best approach.

One drawback is that the Windows Store only lists UWP apps.  It would be nice if they would also distribute desktop apps.  As such, I have to host the app myself.  You can download it from the EP Calipers page.

The program has all the features of the other versions of the app, including the ability to tweak the image rotation, zoom in and out, and load PDF files such as AliveCor™ ECGs.  .NET does not include a native PDF handling library.  In order to load PDF files in EP Calipers for Windows it is necessary to install the GhostScript library.  The free GPL version of the library can be used as EP Calipers uses the open source GNU GPL v3.0 license.  It is necessary to choose whether you are running the 32-bit or 64-bit version of Windows to download the correct version of Ghostscript.  Right-click on This PC and select Properties to see which version of Windows your computer is running.

As always please let me know if you have any problems or suggestions for the program, or for any of the EP Studios apps.  I nearly always incorporate users’ suggestions into these apps, and the apps have benefited greatly from this feedback.  Thanks to everyone who has shared their ideas and opinions with me!

What If My CHA2DS2-VASc Score Is One?

There is nothing simple about atrial fibrillation; it is a complicated, often overwhelming disease, both for patient and physician. One question that invariably comes up early on is the question of prophylactic anticoagulation for prevention of stroke. Who should receive anticoagulation? Which anticoagulant? How should anticoagulation be handled around the time of surgical procedures, or before and after ablation or cardioversion? How should anticoagulation be monitored? How should it be modified in patients with kidney or liver disease? Should anticoagulation be used in patients who have increased bleeding risks? Just the topic of anticoagulation in atrial fibrillation is overwhelming!  Too much for a short blog post. We’ll have to narrow this down further. Let’s talk about using risk scores to decide who should be placed on anticoagulation therapy.

chadsvascAtrial fibrillation risk scores were designed to assess stroke risk in patient populations with atrial fibrillation “without valvular heart disease.” I quoted that because “without valvular heart disease” is not well defined for this purpose. Certainly these risk scores don’t apply to patients with prosthetic heart valves, or with rheumatic mitral stenosis, but beyond that in practice these scores seem to be used even in patients with mild to moderate non-rheumatic valvular disease. The CHADS2 score is very simple, but has become passé in recent years. It is too gross a measure; people with low scores can still be at significant risk for stroke. It has been replaced by the CHA2DS2-VASc score in recently published guidelines. This score makes it much harder to achieve a score of 0 and escape anticoagulation. Using this risk score, both the 2012 European Society of Cardiology (ESC) and 2014 American Heart Association/American College of Cardiology/Heart Rhythm Society (AHA/ACC/HRS) atrial fibrillation guidelines recommend no anticoagulation if the score is zero, and full anticoagulation if it is 2 or greater. Where there is some hesitation, if not disagreement, is when the CHA2DS2-VASc score is 1.  Anticoagulate or not? The previous iteration of the guidelines leaned strongly toward anticoagulation for a CHA2DS2-VASc score of 1. The latest sets of guidelines are more equivocal. How to handle a score of 1 is particularly important when one realizes that female sex, on its own, is a risk factor in CHA2DS2-VASc with a point value of 1. Yes, half the people on the planet are born with a CHA2DS2-VASc score of 1 and by the old guidelines would require anticoagulation just on the basis of their sex.

A Swedish study published in 2012 sheds some light on this issue. The study concluded that, while female sex is a risk factor for stroke in atrial fibrillation if other risk factors are present, by itself, in women less than 65 years old without other risk factors, female sex does not confer a significant risk of stroke. The implication is that a CHA2DS2-VASc score of 1 that is only due to female sex does not warrant anticoagulation.

The results of this study were directly incorporated into the 2012 ESC guidelines (I note that Dr. Gregory Lip is a coauthor of both these guidelines and the Swedish study). Thus the recommendation by the ESC is full anticoagulation (aspirin and aspirin + clopidogrel are relegated to remote second-line therapy) for CHA2DS2-VASc score of 1 or higher, after excluding females with no other risk factors and age < 65 years, who (as with men with the same criteria) do not need anticoagulation.

The AHA/ACC/HRS 2014 atrial fibrillation guidelines are more vague than the ESC guidelines when the CHA2DS2-VASc score precisely equals 1. Cardiology guidelines are presented using a sort of quantified equivocation, with recommendations classified as I (should do it), IIa (reasonable to do it), IIb (you can consider doing it) or III (don’t do it). Not quite orthogonal, there are 3 levels of certainty as well: A (data derived from multiple randomized clinical trials), B (data from one randomized clinical trial), or C (“expert” opinion). Given this, it is interesting that anticoagulation for a CHA2DS2-VASc score of 2 or more is a class I, A level of evidence recommendation, and no anticoagulation for a score of 0 is a class IIa, B level of evidence recommendation. For a CHA2DS2-VASc score of 1 there is complete equivocation, with the following class IIb recommendation:

For patients with nonvalvular AF and a CHA2DS2-VASc score of 1, no antithrombotic therapy or treatment with an oral anticoagulant or aspirin may be considered. (Level of Evidence: C)

Addressing the possibility of a exclusion for females with a CHA2DS2-VASc score of 1, the guidelines state (again equivocating):

"In a study of Swedish patients with nonvalvular AF, women again had a moderately increased stroke risk compared with men; however, women younger than 65 years of age and without other AF risk factors had a low risk for stroke, and it was concluded that anticoagulant treatment was not required. However, the continued evolution of AF-related thromboembolic risk evaluation is needed."

This all creates a problem for physicians, patients (females especially), and also for the physician-programmer writing an app such as EP Mobile that calculates these risk scores and attempts to make recommendations. At present EP Mobile simply uses the old recommendations, as do most of the web-based online risk score calculators I surveyed (e.g. here and here). A user of EP Mobile pointed out to me that its recommendations are out of date.  Trying to fit such complexity into a small dialog box on a smartphone screen is challenging.  Nevertheless I will be updating the app so that its anticoagulation recommendations more precisely match current guidelines — at least until the next set of guidelines comes out.

Introducing EP Calipers

epcalipersicon-180x180Ever since the 1990s, when computer-based electrophysiology (EP) systems were introduced, HV intervals and ventricular tachycardia cycle lengths have been measured in the EP lab by electronic calipers — simple but accurate measurements accomplished on-screen using a track ball or a mouse. Despite this, physicians still often carry a physical pair of calipers, perhaps preserved from the pre-Sunshine Act days when they were provided for free by drug companies. They use these calipers to measure heart rates and QT intervals on printed electrocardiograms (ECGs). But more and more, ECGs are viewed electronically. All physicians now use smart phones and frequently send and receive photos of ECGs or rhythm strips for analysis. For example, when I was on-call there would often be a patient who went into atrial fibrillation in the middle of the night, or a patient who would be due a dose of dofetilide (a potentially dangerous QT interval prolonging drug). The nurse would have a rhythm strip or ECG that needed analyzing and the easiest way to do that in the post-fax machine era was for them to take a photo with a smart phone and text or email it to me for analysis. Measuring heart rates or corrected QT intervals requires the use of calipers, but physical calipers don’t work well with smart phones — maybe even scratching the glass screen! Electronic calipers akin to those used in the EP lab would be useful to make accurate measurements on ECG and rhythm strip images.

I did not realize that there weren’t any apps (as far as I can tell) providing electronic calipers until this was pointed out to me by one of my Twitter buddies, Dr. Michael Katz. So I wrote an app, EP Calipers, that provides these calipers.

Making EP measurements on an iPad
Making EP measurements on an iPad
Measuring RR interval, iPhone 6 Plus
Measuring RR interval, iPhone 6 Plus
Amplitude measurement
Amplitude measurement
QT measurement with QTc calculation
QT measurement with QTc calculation
Multiple calipers, showing heart rate
Multiple calipers, showing heart rate

As the screen shots show, these calipers look just like those provided by EP recording systems, such as the GE (formerly Prucka) Cardiolab system. Multiple calipers can be used at the same time. Both time and amplitude calipers are available.  Unlike real calipers, it is possible to zoom images and make much more accurate measurements. Also unlike real calipers, it is easy to measure mean heart rates and calculate QTc intervals automatically.  The app makes the necessary calculations.

I am hoping these electronic calipers will be easy to use and helpful to anyone who has to deal with ECG recordings. This is the first iteration of the app and I am open to suggestions to improve it. Right now the app is available for Apple iOS (version 8.1 or higher required), but the Android version will be available Real Soon Now. Have fun measuring intervals electronically to your heart’s content!

EP Mobile Update Version 3.6 for Apple Devices

The reviewers at the Apple iTunes App Store have approved the revised version of the EP Mobile app.  For information on why the app needed to be revised, see my earlier posts on the subject.  I removed the drug dose calculators (note though that the Warfarin Clinic module was not removed), but added detailed drug dosing information and a creatinine clearance calculator that can be used while viewing the dosing information.  Other improvements to the app have been made as well.  The changelog is as follows:

Changes from version 3.5
* Removed drug dose calculators as requested by Apple (see developers guide section 22.9)
* Added new drug reference section with creatinine clearance toolbar
* Added creatinine clearance calculator
* Added right ventricular hypertrophy criteria
* Added D'Avila WPW accessory pathway location algorithm

I will release the new version in 2 days (March 22).  If for some reason you can’t live without the drug dose calculators, then don’t update the app.  Turn autoupdate off if it is on to prevent inadvertently updating the app.  Regardless of the lack of drug dose calculators, I encourage most people to update the app, because I think that using the new drug reference information in the app is a better way to determine drug dosages, and because I will continue to add new features to the app, which will not be available to those who do not update.

Note that Android users of EP Mobile still have access to the drug dose calculators, as well as the new features noted above.

I hope that at some point Apple changes its policy and adds physicians to the groups permitted to write apps that calculate drug doses.  After all, it’s what we do.

Countdown to version 3.6 release — Done! Released Mar 22, 2015!

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