Posts tagged “AFIB

STEMI seen in PVC

Although the previous case study was written for formalistic reasons and is admittedly neither very interesting nor particularly original, there is one interesting feature here worthy of note:

The arrows indicate complexes resulting from intermittant LBBB or PVCs with LBBB morphology. The latter is more likely given that their differing frontal plane axes (-60 vs +60) implicate two separate foci.

Despite aberrant conduction, the current of injury resulting from the anterior infarct remains explicit and is diagnostic of coronary occlusion.

In the first EKG (04:15) the complexes in V2 and V3 show appropriately discordant STE, but the ST/S ratio is groselly excessive. In 2010, Dodd and colegues demonstrated that an ST/S ratio >0.2 carries high specificity for LAD occlusion (1). Note the ratios in this case:

V2:    ST/S = 6mm/7mm = ~0.86

V3:    ST/S = 5.5mm/11mm = 0.5

In the second EKG (07:10) there is >1mm concordant STE in V4 and V6. In LBBB, the ST segments should always be discordant, and, when the terminal R wave is positive, they should show an appropriate proportion of ST depression. Thus, even in V6 where the J-point is isoelectric, there is a conspicuous absence of ST depression. This is a STEMI equivalent (2). Even if this patient had a baseline LBBB and the entire EKG showed wide-complex aberrancy, the MI would not be hidden.

These features as illustrated here closely reflect the more thorough and authoratative work of Dr. Smith in his May 21, 2011 blog post, “LBBB: Is There STEMI?

Reproduced from his text:

Smith modified Sgarbossa rule:

  1. At least one lead with concordant STE (Sgarbossa criterion 1) or
  2. At least one lead of V1-V3 with concordant ST depression (Sgarbossa criterion 2) or
  3. Proportionally excessively discordant ST elevation in V1-V4, as defined by an ST/S ratio of equal to or more than 0.20 and at least 2 mm of STE. (this replaces Sgarbossa criterion 3 which uses an absolute of 5mm)


  1. Dodd KW. Aramburo L. Broberg E. Smith SW. For Diagnosis of Acute Anterior Myocardial Infarction Due to Left Anterior Descending Artery Occlusion in Left Bundle Branch Block, High ST/S Ratio Is More Accurate than Convex ST Segment Morphology (Abstract 583).  Academic Emergency Medicine 17(s1):S196; May 2010.
  2. Dodd KW. Aramburo L. Henry TD. Smith SW. Ratio of Discordant ST Segment Elevation or Depression to QRS Complex Amplitude is an Accurate Diagnostic Criterion of Acute Myocardial Infarction in the Presence of Left Bundle Branch Block (Abstract 551).  Circulation October 2008;118 (18 Supplement):S578.
  3. Dr. Stephan Smith. “LBBB: Is There STEMI?” Dr. Smith’s ECG Blog.

Artifact from Frayed Leads Obscures STEMI


Artifactual activity on 12-lead EKG presents a significant impediment to electrocardiographic diagnosis. A case is presented here in which underlying STEMI could not be appreciated due to artifactual interference from frayed electrode leads. Clinicians should to be aware of the causes and presentations of EKG artifact in order to avoid similar pitfalls.


An “all fields” PubMed search was conducted using the term “artifact” in conjunction with each of the terms “STEMI”, “myocardial infarction”, “EKG”, “ECG”, and “ST segment.”  Results yielded 0, 76, 19, 317, and 22 references respectively. These 434 citations were then screened for relevance according to title. The scope of the search spanned from 1973 to June 2012.


Numerous sources and types of artifactual interference on EKG have been identified. Artifact may be defined as any electrical activity present on EKG recording which does not directly and appropriately reflect cardiac activity. Artifactual interference may be classified as either of primary, non-cardiac etiology, or of secondary etiology when authentic cardiac signals are deranged due to incompetent acquisition, processing, or presentation. In the former category, a multitude of electrical and mechanical devices have been implicated (1-12, 46). Movement artifacts such as patient tremor, respiration, coughing, and hiccups have also been described (13-21, 43, 44). Artifact resulting from bed or stretcher movement should also be included in this subgroup.

Regarding the derangement of authentic cardiac signals rather than non-cardiac interference, investigators have noted an extensive variety of effects due to electrode misplacement (25-28, 32, 37). Acquisition filters have also been found to deceptively alter the appearance of the electrocardiogram (30, 33). Inconsistent electrode contacts as well as flawed or inverted lead connections can be problematic (45). Printers, monitors, and electronic transmission software have all been implicated in significant distortion or augmentation of the EKG (29, 41).

Too numerous to count case reports involving both primary non-cardiac interference as well as secondary artifact effects have illustrated a diversity of arrhythmic, ischemic, and other electrocardiographic mimics. Typically low frequency primary artifact resulting from tremors or rhythmic movement of physiologic cycle length has been associated with the mimicry of dysrhymias, often wide complex dysrhthmias (13-21, 23). Derangements of authentic cardiac activity resulting from lead reversals, filtering effects, and post-acquisition processing have frequently been associated with the mimicry of ischemic EKG patterns. The appearance of pathologic Q-waves, dramatic changes in cardiac axis, T-wave deflection, and alterations of R-wave amplitude and progression have been documented (25-27). False ST elevation and depression have also been described (30, 31). Both the masking of intrinsic pathology and the pathologic representation of healthy cardiac signals have been noted (30-34, 40, 45). The consequences of unrecognized artifactual interference can include inappropriate pharmacological and electrical therapies; significant morbidity and mortality has resulted (15, 18, 19, 28).

In some cases, the clinician can exploit artifactual activity. Shivering artifact in the presence of electrocardiographic evidence of hypothermia is such a case (42). The utility of respiratory artifact has also been explored (24). More recently, the exploitation of systematic computer algorithm interpretation error has been discussed relative to “double counting” of heart rate in the setting of hyperkalemia (41).

In this case report, an anterior ST-elevation myocardial infarction was masked by opaque artifactual activity resulting from frayed electrode leads. To date, this would appear to be the first documented case of such an occurrence.

Case Presentation:

An 85 year-old Caucasian man with a history of atrial fibrillation and anxiety awoke at 2:30 AM with chest pressure and shortness of breath. He alerted his daughter and she administered his Xanex, believing his symptoms to be psychosomatic. When this had little effect, an ambulance was called. On their arrival at 3:40 AM, paramedics administered oxygen and 162mg of aspirin. Vital signs at this time were within normal limits. A rhythm strip was acquired which demonstrated heavy artifact obscuring all but one lead. Additional leads were not visualized and no intelligible 12-lead could be obtained.

The patient was transported to a non-PCI capable community hospital. There, a 12-lead EKG was recorded which showed explicit anterior wall STEMI.

The troponin was 0.65. Tenectaplase was administered at 4:30AM; a repeat EKG 90 minutes later was unchanged. At this time, he was transferred to an outside hospital for cardiac catheterization.

On arrival at 7:05AM, the patient was hypotensive with a systolic blood pressure of 70mmHg.

An aortic balloon pump was placed and dopamine initiated. A complete occlusion of the mid-LAD was identified; thrombectomy was performed and the vessel stented with TIMI3 result. Hypotension persisted and the patient developed increasing lethargy and dyspnea. He vomited and became apenic while in cath lab. At 8:15AM he was intubated and placed on levophed; his ejection fraction was less than <15%. Hypotension remained refractory despite the addition of vasopressin and dobutamine. At 10:25AM, the troponin was 92. At this time he was unresponsive on exam with central cyanosis and mottling to all four extremities. There was pulmonary edema with an arterial line indicating a systolic BP of 50mmHg. Blood gas analysis indicated a pH of 7.10. He was described as not likely to survive and made DNR at 10:50AM. At 11:58 AM no carotid pulse could be appreciated and he was pronounced dead.


Retrospective analysis of the prehospital EKG artifact was undertaken. The system was traced from the electrode-lead junctions back to the monitor. In this case, a Physio-Control Life Pack 12 device was being utilized and revealed cable-junction fraying. Experienced operators of this device are often familiar with this type of artifact, and the cable-junction is a known weak point.

Cable fraying or, more broadly, lead-connection artifact, has a distinct electrocardiographic signature. Fequentlely there is an erraticly wandering baseline with sharp, irregular voltage spikes showing inconsistantly varrying amplitudes. As usualy only one connection is effected, the artifact should localize to a particular lead. Thus there should also be leads present which are free of artifact.

Note that in the initial EKG from this case there are voltage spikes of varying amplitudes, a chaotically wandering baseline, and a lead-specific artifact distribution. Other etiologies may mimic lead-connection artifact, but are readily distinguishable once they become familiar to the clinician.

60Hz AC interference should demonstrate almost exactly 60 deflections per second; the baseline typically will not wander and the amplitude will be constant or demonstrate orderly undulation. (Image retrieved from “,”

Artifact from nerve or muscle stimulators should also be of fixed amplitude and hold to a stable baseline. (1)

Shivering artifact may or may not be accompanied by hypothermic ECG stigmata such as bradycardia or Osborne waves; note that the artifact is not confined to any single lead distribution. (Image retrieved from “,”

Artifact from resting tremor is typically of lower (physiologic) frequency and thus can mimic VT or a-flutter; relative to lead-connection artifact, tremor interference is pervasive, consistent, and of much longer cycle length.

The distinguishing hallmarks of lead-connection artifact are,

  1. It is confined to a specific lead distribution– the lead with inconsistent connectivity.
  2. There is a chaotically wandering baseline.
  3. The cycle lengths are short (30-70Hz ?) and grossly irregular.
  4. The amplitude is widely variable and randomly distributed.

When lead-connection artifact is recognized, operators can trouble-shoot the system  for correctable problems. Often a “positional” solution can be temporarily utilized to acquire an acceptable tracing before the cables can be replaced. As in this case, when the origin of the artifact is unknown to the practitioner, it is not possible to investigate such a solution. The tragic coincidence presented here, where in the detection of STEMI was obscured by lead-connection artifact, illustrates that the potential significance of this issue.

While newer lead hardware has been made available, many operators continue to utilize the monitoring cables described in this case.


In this case, an anterior wall STEMI could not be appreciated due to artifactual interference. The patient was therefore transported to a non-PCI capable facility; subsequently, he did not receive definitive reperfusion until nearly five hours after his initial encounter with ACLS providers. The result was a catastrophic infarction from which he could not recover.

Operators should be familiar with the appearance of lead-connection artifact and maintain a high index of suspicion when checking and trouble-shooting this hardware.


  1. Equipment-related electrocardiographic artifacts: causes, characteristics, consequences, and correction. Patel SI, Souter MJ. Anesthesiology. 2008 Jan;108(1):138-48.
  2. Electrocardiographic artifacts during electroconvulsive therapy. Patel SI. J Electrocardiol. 2009 Jul-Aug;42(4):307-9. Epub 2009 Apr 2.
  3. Differential electrocardiographic artifact from implanted thalamic stimulator. Khan IA. Int J Cardiol. 2004 Aug;96(2):285-6. PMID: 15262047
  4. Electrocardiographic artifact caused by extracorporeal roller pump. Kleinman B, Shah K, Belusko R, Blakeman B. J Clin Monit. 1990 Jul;6(3):258-9. PMID: 2380757
  5. Electrocardiogram artifacts caused by deep brain stimulation. Constantoyannis C, Heilbron B, Honey CR. Can J Neurol Sci. 2004 Aug;31(3):343-6.
  6. ECG artifact produced by crystalloid administration through blood/fluid warming sets. Paulsen AW, Pritchard DG. Anesthesiology. 1988 Nov;69(5):803-4. PMID: 3189938 Free full text
  7. Life-threatening ECG artifact during extracorporeal shock wave lithotripsy. Schiller EC, Heerdt P, Roberts J. Anesthesiology. 1988 Mar;68(3):477-8. PMID: 3345012 Free full text
  8. ECG artifact due to deep brain stimulation. Martin WA, Camenzind E, Burkhard PR. Lancet. 2003 Apr 26;361(9367):1431. PMID: 12727397
  9. Electrocardiographic artifact induced by an electrical stimulator implanted for management of neurogenic bladder. Madias JE. J Electrocardiol. 2008 Sep-Oct;41(5):401-3. Epub 2008 Apr 28.
  10. An unusual electrocardiogram artifact: what is its source? [Gastric PM]  J Reddy NK, Merla R, Pehlivanov ND, Pasricha PJ, Ware DL, Birnbaum Y. Electrocardiol. 2005 Oct;38(4):337-9. PMID: 16216608
  11. Unusual ECG artifact. [Infusion Pump] Graham MM. J Nucl Med. 1981 Jul;22(7):660. PMID: 7252570 Free full text
  12. Electromechanical association: a subtle electrocardiogram artifact.[Radial arterial impulse] Aslanger E, Yalin K. J Electrocardiol. 2012 Jan-Feb;45(1):15-7. Epub 2011 Feb 24.
  13. Tremor-induced ECG artifact mimicking ventricular tachycardia. Srikureja W, Darbar D, Reeder GS. Circulation. 2000 Sep 12;102(11):1337-8.
  14. Tremor-related artefact mimicking ventricular tachycardia. Ortega-Carnicer J. Resuscitation. 2005 Jun;65(3):243-4. PMID: 15919558
  15. Parkinson’s tremor mimicking ventricular tachycardia. Bhatia L, Turner DR. Age Ageing. 2005 Jul;34(4):410-1. PMID: 15955765 [Free full text]
  16. Pseudo-ventricular tachycardia: electrocardiographic artefact mimicking non-sustained polymorphic ventricular tachycardia in a patient evaluated for syncope. A Vereckei. Heart. 2004 January; 90(1): 81. PMCID: PMC1768000. [Free Full Text]
  17. Ventricular pseudo-bigeminy due to sustained myoclonus. Chung DK, Reed JR, Chung EK. Heart Lung. 1976 Nov-Dec;5(6):961-3. PMID: 1049219
  18. An unusual case of misdiagnosed ventricular tachycardia. Boos CJ, Khan MY, Thorne SEmerg Med J. 2008 Mar;25(3):173-4.
  19. Pseudo ventricular tachycardia: a case report. Riaz A, Gardezi SK, O’Reilly M. Ir J Med Sci. 2010 Jun;179(2):295-6. Epub 2009 Aug 7. PMID: 19662493
  20. Tremor-induced ECG artifact mimicking ventricular tachycardia. Srikureja W, Darbar D, Reeder GS. Circulation. 2000 Sep 12;102(11):1337-8. PMID: 10982552 Free full text
  21. Tremor-induced ECG artifact mimicking ventricular tachycardia. Freedman B. Circulation. 2001 May 29;103(21):E112-2. PMID: 11382744 Free full text
  22. ECG artifact simulating supraventricular tachycardia during automated percutaneous lumbar discectomy. Lampert BA, Sundstrom FD. Anesth Analg. 1988 Nov;67(11):1096-8. PMID: 3189899
  23. Pseudo-atrial flutter/fibrillation in Parkinson’s disease. Prabhavathi B, Ravindranath KS, Moorthy N, Manjunath CN. Indian Heart J. 2009 May-Jun;61(3):296-7.
  24. The diagnostic use of respiratory artifact. Littmann L. J Electrocardiol. 2010 May-Jun;43(3):264-9. Epub 2009 Dec 2. PMID: 20399349
  25. Capsular contracture simulating myocardial infarction on ECG. Peters W, McEwan PPlast Reconstr Surg. 1993 Mar;91(3):529-32. PMID: 8438025
  26. Influence of electrode misplacement on the electrocardiographic signs of inferior myocardial ischemia. Rudiger A, Schöb L, Follath F. Am J Emerg Med. 2003 Nov;21(7):574-7.
  27. [False diagnosis of myocardial infarction due to inversion of the electrocardiographic leads in the right limbs (author’s transl)]. [Article in Spanish] Guijarro Morales A, Martos Ferrés F, Pagola Vilardebó C, Martín Jiménez V, Martí García JL, Peláez Redondo J. Med Clin (Barc). 1980 May 25;74(10):395-8.
  28. Delayed defibrillation caused by unexpected ECG artifact.[Bad lead selection and artifact] Stewart JA. Ann Emerg Med. 2008 Nov;52(5):515-8. Epub 2008 Apr 3. PMID: 18387704
  29. An unusual ECG artifact–results of a faulty recorder. Agarwal SK. JAMA. 1979 Aug 17;242(7):617-8. PMID: 448997
  30. Electrocardiographic ST-segment depression: confirm, deny, or artifact? [Filters] Wong DH. Anesthesiology. 2008 Aug;109(2):352; author reply 352. PMID: 18648245 Free full text
  31. False ST elevation in a modified 12-lead surface electrocardiogram. Toosi MS, Sochanski MT. J Electrocardiol. 2008 May-Jun;41(3):197-201. Epub 2008 Mar 14. PMID: 18342880
  32. Myocardial infarction or technical artifact? [Electrode misplacement] MacKenzie R. J Insur Med. 2006;38(4):289-92. PMID: 17323759
  33. Simulation of anteroseptal myocardial infarction by electrocardiographic filters. Burri H, Sunthorn H, Shah D. J Electrocardiol. 2006 Jul;39(3):253-8. Epub 2006 Feb 28. PMID: 16777511
  34. Electrocardiographic artifact mimicking acute myocardial infarction. Siddiqui MA, Munugoti S, Khan IA. Int J Cardiol. 2003 Jan;87(1):99-101. PMID: 12468060
  35. Artifactual electrocardiographic change mimicking clinical abnormality on the ECG. Chase C, Brady WJ. Am J Emerg Med. 2000 May;18(3):312-6. PMID: 10830688
  36. An unusual electrocardiogram artifact in a patient with near syncope. Aslanger E. J Electrocardiol. 2010 Nov-Dec;43(6):686-8. Epub 2010 Jun 2. PMID: 20553822
  37. [Brugada or not-Brugada: misdiagnosis of recorder-induced artifact]. [Article in German] Z Kardiol. 2002 Dec;91(12):1061-3. Martius P, Krämer H.
  38. ECG artifacts and heart period variability: don’t miss a beat! Berntson GG, Stowell JR. Psychophysiology. 1998 Jan;35(1):127-32. PMID: 9499713
  39. Pacemaker malfunction: fact or artifact? Murdock DK, Moran JF, Stafford M, King L, Loeb HS, Scanlon PJ. Heart Lung. 1986 Mar;15(2):150-4.  PMID: 3633245
  40. An example of apparently normal electrocardiogram originating from incorrect electrocardiographic acquisition in a patient with ST-segment elevation myocardial infarction. J Electrocardiol. 2010 May-Jun;43(3):222-3. Epub 2010 Mar 23. Aslanger E, Yalin K, Golcuk E, Oncul A.
  41. Double counting of heart rate by interpretation software: a new electrocardiographic sign of severe hyperkalemia. Am J Emerg Med. 2007 Jun;25(5):584-6. Littmann L, Brearley WD Jr, Taylor L 3rd, Monroe MH. PMID: 17543665
  42. Classic EKG changes of hypothermia. Mareedu RK, Grandhe NP, Gangineni S, Quinn DL. Clin Med Res. 2008 Dec;6(3-4):107-8. PMID: 19325173
  43. Common electrocardiographic artifacts mimicking arrhythmias in ambulatory monitoring. Márquez MF, Colín L, Guevara M, Iturralde P, Hermosillo AG. Am Heart J. 2002 Aug;144(2):187-97. PMID: 12177632
  44. Hiccup as an electrocardiographic artifact simulating arrhythmias. Am Heart J. 2003 Oct;146(4):E15; author reply E16. Cheng TO. PMID: 14564338
  45. “The Bait and Switch”. [Limb lead reversal due to inverted lead coupling conceals STEMI] Tom Bouthillet. EMS 12-Lead. 01-22-2011. Retrieved from:
  46. “Unusual EKG/ECG Pattern: You don’t see this everyday”. The Happy Hospitalist. 04-15-2011. Retrieved from:

Case No. 16: Morbid Signature

A 37 year-old Caucasian male presents to the emergency department with palpitations of two hours duration. A 12-lead EKG is recorded.

The man is sedated and cardioversion is performed.

This 12-lead demonstrates an irregularly irregular, polymorphic wide complex tachycardia; this can only be atrial fibrillation with frequent conduction through a Wolf-Parkinson-White accessory pathway system.

The differential diagnosis for this presentation principally consists of polymorphic VT, RVR a-fib with ventricular conduction aberrancy, and a-fib with underlying WPW. The presence of multiple wide complex QRS morphologies excludes the diagnoses of a-fib with BBB, and, as Mattu and Brady have pointed out, polymorphic VT will typically hold a constant rate while this EKG shows significant variance between R-R intervals– from >450ms to <240ms. (Mattu, 2003, p.138)

RVR a-fib with aberrant conduction and gross ST-segment abnormalities but uniform QRS morphology. (EMS 12-Lead:

Polymorphic VT of Torsades de Points in the setting of hypokalemia and prolonged QT; multiple QRS morphologies but uniform rate. (LITFL:

Note that due to the fixed duration of the AV nodal refractory period, synchronized atrio-ventricular conduction is typically limited to below 200 impulses per minute. It is for this reason that RVR a-fib very rarely exceeds 180-200bpm. The bypass tract in WPW, however, has a dangerously short refractory period and thus can support re-entrant tachycardias well above this limit. As Chou has stated, “…the presence of the WPW syndrome can be suspected from the rhythm strip alone if the atrial fibrillation is accompanied by a ventricular rate greater than 200bpm. Such a rapid ventricular response would be highly unusual if the conduction is by way of the normal AV conduction system.” (Chou, 1996, p.480)

Antiarrhythmic agents which slow or block AV nodal conduction are contraindicated in this setting as they can enhance conduction through the accessory pathway and accelerate ventricular response. Procainamide and related sodium channel antagonists have therefore been used with favorable results.

Regarding amiodarone, although numerous case reports have tracked poor outcomes, it remains a popular treatment modality for this syndrome and may statistically be a safe alternative. In 2005, for example, Tijunellis and Herbert demonstrated a case-series of 10 patients in which amiodarone was malignantly proarhythmic; in half of these, the initial arrhythmia was v-fib. Nonetheless, case-series can be misleading and I do not know of definitive research in this area.

In light of this, judicious use of electrical therapy is often considered the safest and most reliable approach.

Mortality associated with the Wolf-Parkinson-White syndrome remains at <1% and is thought to result from rapid response a-fib degenerating into v-fib arrest (Ellis, 2011). This outcome can be fostered through inappropriate pharmacological management if the initial presentation is misunderstood. Fortunately, once this dramatic EKG signature has been appreciated, it is unlikely to go unrecognized.

Dr. Stephen Smith has discussed this syndrome and the treatment risks, and his insights can be found here. Among other remarks, he states, “Atrial fib with WPW is very recognizable: there are bizarre QRS with multiple morphologies, and very fast rhythms with short R-R intervals.  If you can find any R-R interval shorter than 240 ms, then AV nodal blockers are definitely dangerous.” (Smith, 2011)

I wish also to excerpt Dr. Johnson Francis of Cardiophile MD who has addressed this topic directly. Dr. Francis states, “The shortest RR interval gives an estimate of the ventricular refractory period. If it is below 250 msec, it is ominous as the ventricular rates can go very high and it can degenerate into ventricular fibrillation.” (Francis, 2008) Note that in this particular case, the overall ventricular rate is not excessively fast and perhaps speaks to the relative clinical stability of the patient.

Additional case studies of WPW a-fib can be found in the Case Library.


Chou, T. and Knilans, T. (1996). Electrocardiography in Clinical Practice: Adult and Paediatric, 4th Ed. W.B. Saunders Co.

Ellis, C., et al. (2011). Wolff-Parkinson-White Syndrome. Medscape eMedicine. Retrieved from:

Mattu, A. and Brady, W. (2003). ECGs for the emergency physician, V.1. BMJ Publishing Group.

Tijunelis, M. and Herbert, M. (2005). Myth: Intravenous amiodarone is safe in patients with atrial fibrillation and Wolff-Parkinson-White syndrome in the emergency department. Canadian Journal of Emergency Medicine. (4): No.4, p262. Retrieved from:

Case No. 8: “The Great Imitator”

A 52yr old white male with history of heart failure presents to the Emergency Dept. complaining of nausea, vomiting, and a decreased level of consciousness.

Although nearly every imaginable cardiac dysrhythmia has been linked to digitalis poisoning, junctional tachycardia remains uniquely suspicious for this toxidrome. In order to understand the cellular mechanisms connecting digoxin with this and other highly suggestive EKG signatures, the enzyme-level pharmacodynamics must be appreciated.

The direct cardiotonic effects of digitalis arise from inhibition of the transmembrane ion exchange protein, Na+/K+ATPase. Through the exchange of two extracellular potassium ions for three intracellular sodium ions, the phosphorylation of this complex creates a disequilibrium of monovalent cations necessary to the maintenance of the cell’s 80-90mv resting membrane potential.

Fig 1. Conformational shifts of Na+/K+ATPase relative to ion and phosphate binding. Note that the net result of this cycle is the establishment of intracellular hyponatremia.

When digitalis binds to the extracellular surface of the Na+/K+ATPase, a local deformation of the protein’s tertiary structure cripples the ion transport function of the complex [1]. Na+ export is halted and the intracellular environment becomes relatively hypernatremic. This, in turn, exerts a critical effect on yet another ion exchange system—the Na+/Ca2+ antiporter. Normally, the steep Na+ ion concentration gradient across the cell membrane provides an osmotic motive for the Na+/Ca2+ antiporter to drive excess Ca2+ out of the cell. With the Na+/K+ATPase inhibited, however, intra and extracellular sodium concentrations equilibrate. Intracellular calcium levels rise and the sarcoplasmic reticulum becomes over-saturated; cellular depolarization thus triggers a heaver tide of Ca2+ ions and the contractile apparatus responds with greater force.

Fig 2. Inhibition of the Na+/K+ATPase results in elevated intracellular Na+; this stymies the Na+/ Ca2+ exchanger and causes intracellular Ca2+ to rise. Pro-contractile inotropic effects ultimately result.

Yet inhibition of the Na+/K+ATPase has its detriments. With the suppression of normative ion exchange comes a reduction in the ability of the conduction tissues to maintain their 80-90mv membrane resting potential. The gradual influx of cations due to natural membrane permeability cannot be opposed by active transport, and the resting voltage of the intracellular space becomes increasingly positive. As the voltage difference across the cell membrane approaches the trigger threshold of the action potential, the excitability of the conduction tissues rises proportionally. Graphically this can be appreciated below—the slope of the baseline intracellular voltage (phase 4) is seen to rise as cations “leak” into the cell making it less negative. Ultimately, the trigger threshold is reached and the cell depolarizes automatically.

Fig 3. Unipolar recording of a transmembrane action potential from a Purkinje fiber. Control conditions are traced with a solid line, digitalized tissue with dashed line. Note the morphological similarities between the experimental digitalis-altered ST segment presented here and the ST segments seen in the precordial distribution of the case study EKG above.

Due to this effect, digitalis enhances the automaticity of the conduction tissues, encouraging the independent activity of ectopic pacemakers. Depolarization occurs not only more automatically, but also more readily due to the heightened excitability of the cells. This results in a shorter R-T interval and a net positive chronotropic influence. Often in digitalis toxicity the rate of ectopic pacemaker depolarization is accelerated beyond the typical upper limit of the cellular tissue, as seen in the title EKG. Perhaps not ironically given Paracelsus’ adage, “only the dose,” the adverse effects of digitalis toward increased automaticity and excitability, therefore, stem from the same mechanistic activity by which the drug confers its beneficial inotropic influence.

Having thus looked more closely at the direct enzyme-level mechanistics of the cardiac glycosides, it is not surprising to find that the greater portion of dysrhythmias arising from digitalis toxicity consist in ectopic tachycardias such as multifocal atrial tachycardia, junctional tachycardia, and (often bifocal) ventricular tachycardia– as seen below.

Fig 4. Bidirectional ventricular tachycardia. Note the alternating QRS axes and right bundle-branch block type morphology. This occurred in the setting of a supratherapeutic serum level of digoxin as a consequence of acute renal failure.

Yet the mainstay of digitalis pharmacotherapy in the modern era lies in controlling rather than encouraging tachydysrthymias; the treatment of atrial fibrillation, for example, remains central to the role of this drug in the contemporary pharmacopoeia. To explain this seeming contradiction, we must appreciate the scope of the indirect influence in digitalis therapy.

Although less well understood, the anti-chronotropic power of the cardiac glycosides appears to be largely mediated through vagomimetic mechanisms. Increases in efferent vagal impulses, decreases in sympathetic tone, modifications of nerve fiber excitability, and sensitization of arterial baroreceptors have all been described as contributors towards this effect [2]. In supratherapeutic concentrations, the vagal activity of digitalis becomes pathological, giving rise to the bradycardic dysrhythmias—sinus bradycardia and various forms of AV block.

Ultimately what we encounter in digitalis toxicity is a pharmacodynamic system capable of inciting almost any imaginable dysrhythmia and imitating any electrophysiologic pathology. The prevalence of junctional tachycardia in this context may be understood as a logical result of excessive supraventricular vagotonia coupled with enhanced automaticity and excitability of distal ectopic pacemakers.

In the case presented here, laboratory assays returned a substantially elevated serum Digoxin level securing the diagnosis of cardiac glycoside poisoning. This pt. received conservative treatment and was discharged on the third hospital day without incident.


The title of this post is quoted from Louis N. Katz, widely known for his work in electrocardiography. In addition to many articles, he is author of Introduction to the Interpretation of the Electrocardiogram (1952), and Electrocardiography Including an Atlas of Electrocardiograms (1946).

Fig. 1: Graphic on loan via

Fig. 2: Graphic on loan via

Fig. 3: A. Goodman Gilman. The Pharmacological Basis of Therapeutics. Pergamon Press, NY 1990. p. 819.

Fig. 4 and explanatory subtext. Joseph L. Kummer. Bidirectional Ventricular Tachycardia Caused by Digitalis Toxicity. Circulation. 2006; 113:p156-156.

[1] In depth discussion of the molecular mechanistics involved with glycoside / ATPase binding can be explored via H. Ogawa et al. Crystal Structure of the Sodium-Potassium Pump with Bound Potassium and Ouabain. Proceedings of the National Academy of Science, Vol. 106, No. 33, 2009, pp.13742-13747. See also, S.M. Keenan et al. Elucidation of the NaKATPase Digitalis Binding Site. Journal of Molecular Graphics and Modeling, Vol. 23, 1995, pp.465-475.

[2] A. Goodman Gilman, Pp. 814-829.

As a final note, due to the nature of this material the account presented here is necessarily simplified and incomplete in many respects; further inquiry can be well satisfied via A. Goodman Gilman, Lipman-Massie Clinical Electrocardiography, Goldfrank’s  Toxicologic Emergencies, as well as other more detailed resources.

Case No. 4 E: Pain Free

A 52 yr old man, transfered from an outside hospital, pain free at this time and resting comfortably.

Included for completeness, this ECG demonstrates no AV block but is a distractor from the previous series. Individual P-waves cannot be identified; the rhythm is irregularly irregular. In the context of inferior wall MI, this pt is experiencing slow ventricular response a-fib with an associated digitalis-type ST-segment morphology.

Again, unfortunately, no follow up was possible regarding this pt’s outcome.