In April of 2011 I presented a case of subtle hyperkalemia. A reader, Dr. George Nikolic, author of Practical Cardiology 2nd Ed., responded with the following commentary,
“The QT is unusually long for hyperkalemia; the lady may have additional pathology (e.g., myxoedema) or be on some QT prolonging medication. The commonest cause of low voltage is large or multiple infarcts in the past. What were her other medical problems?”
I was unable to follow up on this case until recently. Here is what I uncovered:
The patient was an 81 year-old caucasian female nursing home resident of unknown social background with a past history of hypertension, dyslipidemia, diabetes, colon cancer (s/p diverting ileostomy), depression and dementia. Despite numerous cardiac risk factors, she had no explicit history of myocardial infarction, coronary disease, or CHF. There was no history of thyroid disease or obesity.
Her medications consisted of Lexapro 10mg, Aricept 5mg q.h.s, Lopressor 12.5mg b.i.d., folic acid, and Imdur 30mg daily.
She had visited the Emergency Department 12 days prior to this episode with complains of weakness and bradycardia. At that time her BUN was 22, Creatinine 0.8, Sodium 136, Potassium 3.7, and Calcium 9.1. The following EKG was recorded:
Cardiology was consulted and a differential of sick-sinus syndrome vs. beta-blocker toxicity was considered. The Lopressor was reduced, and, following a 48-hour admission, she was discharged back to the nursing home with a slightly increased heart rate.
Two weeks later, on the date in question, she again presented to the ED with complaints of syncope and generalized weakness. This EKG was recorded on arrival:
The hospitalist’s admission note described a provisional diagnosis of acute renal failure secondary to dehydration and possible UTI. Obstructive failure was also considered in light of the cancer history. Most revealing, a thorough chart review revealed two prior admissions for acute renal failure secondary to dehydration from high-output ileostomy syndrome.
Echocardiography on the second hospital day reported no chamber enlargement, no increased wall thickness, no wall motion abnormalities, no valvular disease, no pericardial or pleural effusion, and a normal systolic function with an EF > 55%.
On the third hospital day she was discharged back to her nursing facility with the following EKG:
The differential diagnosis for low voltage is broad; neoplastic, metabolic, autoimmune, infectious, genetic, and acquired disease states are all represented.
When bradycardia is added, the field narrows: thyroid disease, acute or chronic ischemia, and hypothermia are among the most common etiologies.
In hyperkalemia, it is traditionally understood that when the QRS is normal, the QTc should be either shortened or unremarkable. (Smith, Jan 12, 2010; Lipman-Massie, p.579) In this case, the QTc at 6.4mEq K+ (394) is practically identical to the QTc at 4.0 mEq K+ (394). I do not know if the GE-Marquette algorithm uses the Bazett formula for QTc, but this formula is known to under-correct at abnormally low heart rates. (Wikipedia, 2012) Therefore, although the QTc here may be longer than the computer estimates, in an adult female, a QTc of 395 remains if anything on the short side of normal. Regarding medications, however, Lexapro is known to cause QT prolongation.
There was no effusion, as I had originally hypothesized in 2011. We do not have a solid culprit for the low voltage. The QT looks relatively normal. I am grateful for Dr. Nikolic’s attention and comments regarding this case. Fortunately for the patient, the clinical correlations do not seem to support either of our theories.
Dunn, B. and Lipman, B. (1989) Lipman-Massie Clinical Electrocardiography, 8th Ed. Yearbook Medical Publisher Inc.
Smith, S. (2010) Hyperkalemia with cardiac arrest. Peaked T waves: hyperacute (STEMI) vs. early repolarization vs. hyperkalemia. http://hqmeded-ecg.blogspot.com/2010/01/peaked-t-waves-hyperacute-stemi-vs.html
Wikipedia. (2012) QT interval. http://en.wikipedia.org/wiki/QT_interval
In 2007, Littmann and colleagues presented a novel EKG indicator of hyperkalemia based on the computerized “double counting” of heart rate. Over a 13-year period they identified 33 cases in which the GE-Marquette computerized 12SL EKG interpretation algorithm “double counted” or “near double counted” the actual heart rate seen on electrocardiogram. All 33 patients had hyperkalemia (between 5.3-8.8 mEq/L K+) as confirmed by serology taken within two hours of the double-counted EKG recording.
Littmann’s sign can be seen in the following EKG, initially presented here as a study in hyperkalemia in September of 2010.
A 65 year-old Caucasian man with sepsis and HHNKC; the potassium was 7.7mEq/L. The heart rate is 72 bpm; the computer counts 137 bpm.
Although the GE algorithm is proprietary and unavailable for analysis, they argue that, “The QRS width and axis measurement by the interpretation software suggested that, on many occasions, the computer recognized the T waves as being the QRS complexes….” (p.586)
Littmann et al. conclude stating, “Although interpretation software double counting of heart rate appears to be quite specific for hyperkalemia, its sensitivity is almost certainly very low.” (p.586)
While this research represents an intriguing new insight, it leaves many open questions. How were these 33 EKG cases identified? Were certain populations screened for this anomaly? How many total EKGs were reviewed in the course of this investigation?
Littmann claims that double counting “appears to be quite specific” presumably because all 33 EKGs were associated with underlying hyperkalemia. Yet without insight into the methods used to assemble this case series, I remain skeptical that these investigators did not succumb to confirmation bias in the process of collecting their EKGs. The existence of non-hyperkalemic double counting is not discussed in this publication and no differential diagnosis is presented regarding alternative etiologies.
In fact, concerning alternative etiologies and the specificity of double QRS counting, it turns out that this phenomenon has been extensively described in the pacemaker literature for over a decade. A Pubmed search using the combined terms “double counting QRS” produces numerous references. (Al-Ahmad A, Barold SS, Boriani G)
I reviewed 22 pacemaker EKGs collected over a 10 month period, recorded pre-hospitaly using the same GE-Marquette algorithm. This is what I found:
Looking further through ~50 EKGs collected over the same 10 months I found this as well:
In the first pair of EKGs, the computer appears to be confusing the pacemaker spike for a QRS complex; this is clearly “double counting of the QRS.”
The second pair is more complicated. This is not technically “double counting” of the QRS; there is not a 1:1 relationship between each QRS and a particular artifactual deflection. This is over-counting with a coincidental but not precise 2:1 relationship between the total count made by the computer and the total number of true QRS complexes. The interpretation of “Atrial Fibrillation” supports this in that it suggests that numerous complexes are counted during the first 5 seconds and then much fewer in the last 5. Although Littmann’s sign is not technically present here, the 12-lead EKG must be scrutinized to reach this conclusion. This seems problematic given Littmann’s stated goal of elucidating an “objective”, and “easily identifiable” indicator. (p.586)
No clinical data is available on these EKGs and it cannot be proven that these patients did not in fact have elevated potassium.
While producing these two hypothetical “false positives” hardly constitutes significant evidence, it is interesting that such counterpoints to Littmann’s specificity claims were so easily identified. Of further concern is the distinction between perfect double counting as seen in the pacemaker case and “near double counting” as seen in both the hyperkalemia case from Sept. 2010 and artifact case. What bearing this has on Littmann’s argument remains unclear.
Although a novel indicator, I am not sure that there is as yet persuasive evidence for what exactly Littmann’s sign indicates or how often this indication is specific for any one underlying clinical etiology.
Littmann L, Brearley WD, Taylor L, Monroe MH. Double counting of heart rate by interpretation software: a new electrocardiographic sign of severe hyperkalemia. Am J Emerg Med 2007;25:584-90.
Tomcsányi J, Wágner V, Bózsik B. Littmann sign in hyperkalemia: double counting of heart rate. Am J Emerg Med. 2007 Nov;25(9):1077-8.
Al-Ahmad A, Wang PJ, Homoud MK, Estes NA 3rd, Link MS. Frequent ICD shocks due to double sensing in patients with bi-ventricular implantable cardioverter defibrillators. J Interv Card Electrophysiol. 2003 Dec;9(3):377-81.
Barold SS, Herweg B, Gallardo I. Double counting of the ventricular electrogram in biventricular pacemakers and ICDs. Pacing Clin Electrophysiol. 2003 Aug;26(8):1645-8.
Boriani G, Biffi M, Frabetti L, Parlapiano M, Galli R, Branzi A, Magnani B. Cardioverter-defibrillator oversensing due to double counting of ventricular tachycardia electrograms. Int J Cardiol. 1998 Sep 1;66(1):91-5.
An 81 yr old white female with multiple medical problems presents to the ED complaining only of syncope and weakness; the routine 12-lead EKG is pictured below.
Yet the most remarkable feature of this case is the disarmingly low voltage. Although the electrocardiographic attributes of hyperkalemia remain well exemplified (peaked, sharply pointed T-waves, bradycardia, and a somewhat elongated PR interval), the attention-grabbing mountainous T-waves are conspicuously absent. This is because the EKG must be seen in the context of its own voltage. When viewed against the background of the low-voltage QRS amplitude, the T-waves are proportionally massive, just as in the classic case. Given the considerable incidence of pericardial effusion in pts with renal disease, it is not unreasonable to imagine both of these pathologies contributing to the appearance of this electrocardiogram.
In this case, laboratory assays returned showing a potassium level of 6.4 mEq/L; the pt was temporized in the ED and ultimately admitted for further evaluation. The presence or absence of pericardial effusion could not be confirmed.
Over the past year a variety of superior resources have been released dealing with the problem of critical hyperkalemia, its electrocardiographic manifestations, and its treatment. As it would be a great challenge to improve on what has been done here, I am simply going to replicate the links below.
Link No. 1: Dr. Stephan Smith of Dr. Smith’s ECG Blog has posted a video covering 4 critical hyperkalemia cases with notable EKG presentations. Be sure to take a look at his first case, second EKG, for a valuable signature morphology which can easily be misinterpreted as STE anterior MI.
Link No. 4: Scott Weingart of the EMCrit Podcast has released an incisive 15-minute Pod-Cast covering cutting edge hyperkalemia treatment paradigms. There may be some practice-changing insights here, so check it out.
Link No. 5: Jeffrey Guy of the Surgery ICU Rounds Podcast has a 30-minute overview and discussion of hyperkalemia, normal potassium physiology, and treatment approaches. This is a hospital/ICU-oriented discussion addressing burn medicine, trauma, rhabdomyolysis, etc. More in-depth, more information.
Please feel free to suggest additional resources; also note that the September 2010 case study published here, “Unconscious with Wide Complex Rhythm,” involves a more comprehensive discussion of hyperkalemic EKG changes.
The differential diagnosis for this patient’s EKGs includes acute MI, historical MI with left ventricular aneurysm, reperfusion effects, and acute neurological catastrophe with catecholaminergic stress pattern.
On the left is a normal (80%) Right-Dominant coronary system showing the PDA branching from the RCA. On the right is a volume rendered CT image demonstrating a Left-Dominant system with the PDA (arrowhead) and a posterolateral branch (white arrow) arising from the circumflex (black arrow). 
Inferolateral STEMI secondary to Left-Dominant LCx occlusion showing reciprocal depressions across the anterior leads.
A proximal occlusion of a wraparound LAD resulting in an “inferoanterior” STE pattern could also be hypothesized, perhaps with greater similarity to the case study EKGs, and a good case report of this phenomenon with angiographic evidence can be found in Akdemir et al. (2005). The graphic bellow illustrates the interpretive advantages of such a theory.
Note that the inferior elevations in both this case from Akdemir et al. and in the title EKGs are most apparent in aVF. Given that aVF views the inferior apical region, elevation seen here might be considered contiguous and consistent with elevations in V2-5 looking at the anterior wall. The territory of infarction can then be seen as a continuous band, reaching down the path of the wraparound LAD, down the anterior wall, and curling under the heart to the inferior wall.
Ultimately the diagnosis of STEMI would command greater credence here were there clearly pronounced reciprocal changes in corresponding leads. While in the first EKG one can imagine a fraction of a millimeter of ST depression in aVL, there are no explicit reciprocal depressions and the global T-wave inversions cannot be accorded any significance in this regard. Rather, if committed to the diagnosis of STEMI, the T-wave inversions might be considered a Wellenoid feature, perhaps suggesting a prodrome of isolated T inversions which has subsequently evolved into acute STE. Lastly, the case for AMI is supported by the prolonged QT interval, although this remains a non-specific factor.
On consultation with Tom Bouthillet of EMS 12-Lead, it was suggested that a reperfusion T-wave pattern might help to explain some of what is seen here. This view is attractive from a morphological standpoint and can perhaps be best explicated via comparison with an exemplar case as seen below.
This EKG represents post-reperfusion of a 100% occluded wraparound LAD; Dr Smith (2011) states, “There are “reperfusion” T-waves in V1-V6 and I, aVL. There is a QS-wave in V2, and QR-wave in aVL, and poor R-wave progression in V3 and V4, all diagnostic of anterolateral MI, subacute.”
As in this EKG from Dr. Smith, the QS complexes and obliteration of R-wave progression from the case study tracings raises suspicion of a subacute or chronic pathology. In conjunction with the concave downward ST segment morphology, an extinction of anterior electrical forces with deep pathologic Q-waves suggests the possibility of persistent ST elevation due to prior MI and LV aneurism. Dr. Smith (2005) has proposed a formula for the differentiation of anterior STEMI from persistent STE secondary to historical MI premised on the ratio of the T-wave to the QRS amplitude; qualitatively, AMI should present with large T-wave amplitude relative to the QRS, while LV aneurysm should demonstrate a comparatively lower T/QRS ratio. Smith states, “the T/QRS ratio in any one of leads V1-V4 was almost always higher than 0.36 in acute MI, and almost always lower in LV aneurysm. Better was a T amplitude (V1+V2+V3+V4) / QRS amplitude (V1+V2+V3+V4) <> 0.22.”
Applying this rule to the initial case study EKG, (V1-1.5mm, V2-2mm, V3-3mm, V4-4.5mm) / (10mm, 23mm, 21mm, 12mm) = 0.16. Biphasic or inverted T-waves are unlikely in AMI, yet they are not uncommon in LVA. Observe the ST morphology and T-wave inversions in the EKG below.
In their 2008 case study, Biyik et al. captured this EKG, stating, “Thirty days after myocardial infarction, echocardiography revealed an akinetic apical aneurysm, anterolateral hypokinesia of the left ventricle, and decreased ejection fraction (45%).”
Both the results from the Smith formula and comparison with the EKG above point away from AMI and more toward a historical MI w/ LVA. It has been suggested, however, that a tall R-wave in aVR may be correlated with aneurysm; the absence of this finding here is of unclear significance but perhaps counts against the mounting argument for LVA.
Lastly, global, deep symmetric T-wave inversions transgressing multiple territories of coronary perfusion have long been documented in the setting of acute neurological catastrophe. Inferoanterior ST elevation and prolonged QT have also been described in this context, specifically with regard to Takotsubo syndrome, and can be seen below.
A patient with Takotsubo cardiomyopathy demonstrating ST elevation in anterior and inferior leads. 
Top represents a pt’s baseline EKG with QTc of 407; bottom is the same pt., now with echocardiographic evidence of Takotsubo syndrome, showing diffuse T-wave inversions and a prolonged QTc calculated at 519. 
The mechanism of these neurogenic EKG manifestations is believed to result from an autonomicaly mediated catecholamine surge leading to transient coronary vasospasm and myocardial ischemia. The case study, “Status post arrest, now with transtentorial herniation,” from September 2010 of The Jarvik 7 discusses this issue at greater length, and it should be noted that the ST deflections in the 2010 case are comparably global in distribution, again showing incongruity with traditional zones of coronary perfusion.
Returning, however, to Biyik’s 2008 case, it is not surprising to find a correlation between LV aneurysm morphology and neurogenic stress cardiomyopathy. An LVA electrocardiographic overlay may reflect the physiological reality that Takotsubo syndrome is partly characterized by a “ballooning” or temporary aneurysm of the apical region of the left ventricle. In this case, Biyik reports of a 35yr male presenting with intense agitation following a narrowly avoided attempt on his life. Future inquiry and systematic literature review may yield confirmation of this relationship and further insight into the mechanisms involved.
In the absence of clinical context or additional test results, these EKGs present a challenging electrocardiographic differential diagnosis. By morphological as well as mathematical criteria, the anterior leads are suggestive of LVA, yet the limb leads betray additional findings which demand a more inclusive pathophysiology. In light of the arguments explored above—principally the suspiciously non-localized ST and T-wave abnormalities coupled with the morphological elements of the T inversions—the case for an ischemic stress pattern may carry the most persuasive weight.
As always, comments and additional observations are welcome. I am indebted to both Tom Bouthillet and Dr. Steven Smith for consultation on this case.
Smith, S. (2011). Hyperacute T-waves, missed by computer, short DTB, but large myocardial infarction. Dr. Smith’s EKG Blog. Retrieved from http://hqmeded-ecg.blogspot.com/2011/01/hyperacute-t-waves-missed-by-computer.html.
 Tomich et. al.
 Wong, A. et al. (2010). Preoperative takotsubo cardiomyopathy identified in the operating room before induction of anesthesia. Anesthesia & Analgesia, 110(3), 712-715. doi: 10.1213/ane.0b013e3181b48594
A 68yr long-term care inmate presented to nursing with an altered level of consciousness, chest pain, and bradycardia. Paramedic services were called to the scene for transport and found the nursing staff encouraging the pt to walk back and forth across the exam room to, “help bring his pulse up.” The following EKG was recorded. Note that voltage enhancement has been maximized in the rhythm strip to 2cm/mv, while the 12-lead is displayed with the standard gain of 10mm/mv.
As this is a third party case, little direct clinical or situational information is available to contextualize this EKG or the surrounding events. Objectively speaking, a markedly bradycardic junctional rhythm can be appreciated with retrograde conduction of p-waves, seen inverted, buried 160ms into the QRS complex. Net positive QRS deflections in I-III, avL and avF, and negative in avR indicate an axis in the lower left quadrant. Close examination reveals a 0.1mv electrical alternans, perhaps most evident in the limb leads, but also apparent (~0.05mv) in V5 and V6. Explicitly pathological features include subtle precordial T-wave inversions in V1-3 and conspicuous low voltage QRS amplitude in all leads.
Regarding this latter subject, numerous criteria have been suggested as to what constitutes abnormally low voltage; a consensus approach would consider either the sum of the QRS voltages in all 12 leads as necessarily less than 12mv, or a combined judgment requiring the average of QRS voltages in the limb leads as less than 5mm and that in the precordial leads less than 10mm.
The typical differential diagnosis associated with low voltage QRS includes etiologies of increased impedance (such as obesity, hyperinflative lung disease, and pericardial/pleural effusion), etiologies of infiltrative disease (such as hemochromatosis, amyloidosis, and neoplasm), and metabolic or toxicological causes (such as hypothyroidism and alcoholism). Low voltage has also been associated with both chronic and acute ischemic heart disease. An exhaustive review of the DDx can be found here.
While neither the clinical nor the electrocardiographic features of this case are sufficiently specific to seal any one diagnostic verdict, there are nonetheless some possibilities here worthy of note. Exogenous toxicological etiologies should be ruled out; hypotension with a slow junctional escape could be linked to digitalis, beta and calcium channel blockers, or other readily available pharmaceuticals. Of particular interest, the possibility of RCA associated ischemia must also be entertained. The pt’s clinical picture, low voltage QRS amplitude, and junctional bradycardia are strongly suggestive in this direction. Similar presentations with more explicit pathological substrates can be seen on this site in case nos. 4A- 4D, particularly the slow junctional STEMI of no. 4D.
Lastly, the subtle finding of electrical alternans forces a compelling consideration of pericardial effusion. Were the heart indeed spatially shifting within the pericardium from beat to beat, one would anticipate a greater shift of axis in the frontal, limb-lead plane than the transverse plane of the precordial leads, just as is present on this tracing. Alternating junctional foci or an artifact of physical positioning could produce a similar bigeminal effect, yet when this alternans is seen in the context of low voltage, the finding commands greater attention.
Paramedic services successfully temporized this pt’s status with atropine and supportive care until he reached the emergency department; there, after 20 minutes, he receded into semi-consciousness. No follow-up could be done.
This patient is a 64 year-old cachectic white male, admitted to ICU with a five day history of nausea, vomiting, and upper abdominal discomfort. The following EKGs were collected in the ED before and after treatment. His history includes HTN, alcoholism, and IDDM.
Classic electrocardiographic indications of hyperkalemia include sharply peaked, symmetrical T-waves, suppression of atrial activity, bradycardia, a markedly widened QRS and a short QT interval. Note how the rhythm in this case approaches the appearance of a sign wave as the QT narrows and the ventricular complexes widen; this is representative of the course in worsening hyperkalemia and is sometimes responsible for the idoventricular or agonal appearance of some hyperkalemic EKGs. This should not be considered a mere “agonal appearance,” however, as typically broad and flattened P-waves with an elongated PR interval will progress toward complete atrial paralysis, frank idoventricular activity below 40bpm, and subsequent hemodynamic collapse.
Distinguishing between the T-wave morphologies of hyperkaemia, early-repolarization, and hyperacuity in early MI can become problematic for pt. outcomes in the acute setting, particularly in the latter case, and a good discussion of this issue can be found at Dr. Smith’s EKG blog. It has been said that hyperkalemic T-waves are “tented” and should be pointed enough to prick your finger. Also note Lipman and Massie’s observation that, “The uniformly wide complex in hyperkalemia differs from the wide QRS in bundle branch block (terminal QRS sluring) or pre-excitation (initial sluring) in that the uniform widening of the QRS in hyperpotassemia affects both the initial and terminal QRS portions.” Lab values are as follows:
Despite resuscitation in the ED this patient arrived in the ICU with a BP of 70/40, HR 60bpm, RR of 30, and a room air SpO2 of 88%. The patient was ultimately stabilized over a matter of days but required extensive pressor support for evolving bacteremia and HHNKC. An ultrasound of the upper abdomen revealed fatty infiltration of the liver but no cholecystitis or cholangitis. It should be noted that although a history of recent complaints could be obtained from the patient’s family members, he initially presented in a comatose state.
Of additional relevance in this case may be Lipman-Massie’s further contention that, “Low sodium levels tend to exaggerate and high sodium levels tend to neutralize the ECG effects of hyperpotassemia.”
Dramatic recordings of progressing or resolving hyperkalemia are not difficult to find about the internet. Dr. M. Rosengarten has a fine series here.
Quotations from Lipman-Massie Clinical Electrocardiography, 8th Ed. Marvin I. Dunn MD, Bernard S. Lipman MD. Yearbook Medical Publisher Inc. ©1989. See pp. 240-243.