Color Atlas and Synopsis of Electrophysiology, 1st Ed.


Richard Bayer II, MD, and Michael Gold, MD


A 20-year-old woman with a medical history of only a recent urinary tract infection presented to the emergency department for evaluation of palpitations. While in the waiting room the patient suffered a witnessed cardiac arrest. A code was called and cardiopulmonary resuscitation (CPR) was begun. Upon arrival of the code team, she was noted to be in ventricular tachycardia (Figure 63-1) and was externally defibrillated to normal sinus rhythm. Subsequent 12-lead ECG (Figure 63-2) demonstrated a prolonged QT interval with a QTc of 640 ms. She continued to have frequent episodes of ventricular tachycardia that were refractory to magnesium and amiodarone infusion but responsive to lidocaine. Further interviewing of the family revealed that the patient had been started on levofloxacin 3 days prior for a urinary tract infection. At this time the levofloxacin was discontinued, and trimethoprim/sulfamethoxazole was substituted. She was monitored in the cardiac critical care unit where she continued to have nonsustained runs of ventricular tachycardia of decreasing frequency over the next 48 hours. The lidocaine was discontinued, and her QTc shortened and eventually returned to normal (Figure 63-3). After 3 days of observation, she demonstrated no further episodes of ventricular tachycardia. She was discharged home and at follow-up had a normal 12-lead ECG including a normal QT interval.


FIGURE 63-1 Initial rhythm seen on rhythm strip following witnessed arrest.


FIGURE 63-2 Initial 12-lead ECG following defibrillation.


FIGURE 63-3 Twelve-lead ECG several days following cessation of levofloxacin.

A 60-year-old man with a known medical history of coronary artery disease, previous stent to the left anterior descending coronary artery with a chronically occluded right coronary artery, hypertension, hyperlipidemia, diabetes, and an ischemic cardiomyopathy with an ejection fraction (EF) of 40% presents after an out-of-hospital cardiac arrest. He was playing golf with a friend when he was noted to suddenly collapse. CPR was initiated and EMS was contacted. An automatic external defibrillator (AED) was available and was used to defibrillate the patient. Interrogation of the AED revealed the patient to be in ventricular tachycardia (Figure 63-4). Upon arrival to the emergency department, routine laboratory work revealed a low potassium level of 3.2 mmol/L. The patient was started on potassium replacement, and a single chamber implantable cardiac defibrillator (ICD) was placed. At follow-up, his potassium level had remained in the normal range; however, interrogation of his ICD revealed several episodes of ventricular tachycardia that were pace-terminated.


FIGURE 63-4 Rhythm strip of initial rhythm prompting defibrillation from AED.


There are several mechanisms by which sudden cardiac death (ventricular tachycardia/ventricular fibrillation [VT/VF]) can be can be caused by potentially reversible causes. The most common of these include electrolyte imbalances, drugs, and ischemia.1

Electrolyte Abnormalities


Hypokalemia is a common electrolyte abnormality that is encountered during clinical practice. It can be observed in as many as 20% of hospitalized patients.2 This prevalence is notable among cardiac patients, as the most common cause of hypokalemia is the use of diuretics, mainstay therapy for hypertension and heart failure.2 See Table 63-1 for major causes of hypokalemia.

TABLE 63-1 Major Causes of Hypokalemia

Causes of Hypokalemia


Renal losses

• Diuretic use

• Renal tubular acidosis

• Hypomagnesemia

• Mineralocorticoid excess

Gastrointestinal loses

• Diarrhea

• Emesis

• Laxatives

• Drainage (naso-gastric tube, G-tube, etc.)

Intracellular shift

• Alkalosis

• Excess insulin

• Hypothermia

• Use of beta-agonists

Potassium is necessary in the maintenance of the cardiac myocyte resting transmembrane potential as well as repolarization of the cardiac action potential3,4 (Figure 63-5). As such, alterations in the serum potassium concentration can have important cellular electrophysiolgic effects. Specifically, low serum potassium concentrations decrease the outward delayed rectifier current (IKr), prolonging repolarization.3This may occur through internalization and degradation of the HERG channels that are responsible for IKr, which has been demonstrated to occur at low serum potassium concentrations.5 The electrocardiographic results of hypokalemia can be prolongation of the QT interval predisposing to malignant ventricular arrhythmias and torsades de pointes.3,5


FIGURE 63-5 Cardiac action potential with ion movements during the various phases. Sodium and calcium ions entering the cell; potassium ions moving out of the cell during repolarization.


While not as common as hypokalemia, hyperkalemia can occur in up to 8% of hospitalized patients. Hyperkalemia is most commonly observed in patients with renal insufficiency and as a consequence of medications.6 Please see Table 63-2 for causes of hyperkalemia.

TABLE 63-2 Major Causes of Hyperkalemia

Causes of Hypokalemia


Reduced excretion

• Acute and chronic kidney disease

• Aldoseterone deficiency

• Volume depletion

Extracellular shift

• Acidosis

• Hyperglycemia

• Beta blockers

• Exercise


• Digoxin

• SuccinyIcholine

• Calcineurin inhibitors

• Minoxidil

The cardiac myocyte resting membrane potential is maintained at approximately –90 mV.3 As extracellular potassium levels increase, as in the setting of hyperkalemia, the resting membrane potential decreases. This change in resting membrane potential affects the number of voltage gated sodium channels available for activation during phase 0 of the action potential. As the number of sodium channels available decreases, the magnitude of the inward sodium current decreases, resulting in slowing of impulse propagation and prolongation of membrane depolarization. As potassium levels continue to rise, membrane depolarization continues to lengthen with widening of the QRS and eventual merging with the T wave, producing a sine wave pattern. Once this is observed, without normalization of the potassium level, ventricular fibrillation and asystole are almost certain.7


Hypomagnesemia is another frequently occurring electrolyte abnormality, occurring in up to 12% of hospitalized patients.8 Similar to potassium, the use of diuretics, both loop and thiazide-type, can result in renal magnesium wasting.9 Other medications, such as the frequently prescribed proton pump inhibitors, can also cause hypomagnesaemia through decreased absorption.10

The effects of magnesium on the cardiac action potential most likely occurs through its interactions with the ion channels of other cations. Magnesium within the cardiac cell functions to block cellular potassium channels thus limiting efflux of intracellular potassium. This action is crucial in promoting the potassium flow that comprises the inward rectification current.11 Magnesium also influences calcium movement through L-type Ca++ channels, which work with the rectification current to maintain the phase 2 plateau of the cardiac action potential.3,11 Increase in either of these currents, resulting from magnesium depletion, decreases the cardiac action potential and thus increases susceptibility to arrhythmias.12


Hypocalcemia is most frequently encountered in patients with chronic renal insufficiency.6 During phase 2 of the cardiac action potential, influx of calcium though L-type Ca++ channels balances outward movement of potassium, which produces the plateau phase.3 A low extracellular calcium level decreases this inward flow. This decreased inward flow of calcium works also to decrease the outward flux of potassium and functions to prolong the action potential. The end result is prolongation of the QT interval and risk for the development of torsades de pointes.6

Medications and Drugs

Both prescription medications as well as illicit drugs can cause VT and VF through a variety of mechanisms.

Acquired Long QT

The exact incidence of drug-induced long QT and subsequent development of torsades de pointes is largely unknown. According to data from the World Health Organization Drug Monitoring Centre, there were 761 cases of drug-induced torsades de pointes reported between 1983 and 1999. Of these 761 cases, 34 were fatal. However, there is some speculation that due to variable reporting this voluntary reporting system may underestimate the true incidence by as much as 10-fold.13 A large population-based case-control study conducted in the Netherlands demonstrated a significant increase in the risk of sudden cardiac death with current use of any noncardiac QT-prolonging drug with an odds ratio of 2.7. However, the overall incidence was still quite low with only 24/775 cases currently using a noncardiac QT-prolonging drug.14

The most common mechanism by which medications prolong the QT interval is through blockade of the potassium channel encoded by the HERG gene.3,13 Blockade of this channel results in decreased potassium efflux, IKr, prolonging repolarization and phase 3 of the action potential. Prolongation of repolarization in turn leaves myocardial cells susceptible to early afterdepolarizations, resulting in triggered activity. In the right environment, this triggered activity can then result in reentry and perpetuation of torsades de pointes.13 This effect may be further modulated by serum potassium concentrations. As serum potassium levels decrease the blocking effect of the drug on IKr is enhanced. This results in a further increase in the duration of repolarization and a subsequent increase in the risk of development of torsades de pointes. However, at higher potassium concentrations the blocking effects on IKrare attenuated, less QT prolongation is seen, and the risk of torsades de pointes is lessened.15

Sodium Channel Blockers

Drugs that block sodium channels can perpetuate VT or VF via a different mechanism. By blocking sodium channels, conduction is slowed via prolongation of rapid depolarization, phase 0 of the action potential.3,16 In this setting, reentry may be perpetuated because with slower conduction a propagating wavefront of depolarization is less likely to encounter refractory myocardium and in turn be quenched. In patients with circuits for reentry, such as scar formation from ischemic heart disease, this has the potential to sustain reentry and thus VT. While this VT is frequently slower, it has the potential to degenerate into slow VF that can be highly resistant to cardioversion.16


Cocaine is the most frequently abused illicit drug that results in emergency department visits in the United States. In 2011, it was responsible for just over 40% of the 1.25 million emergency department visits involving illicit drugs.17

Cocaine can cause sudden cardiac death through multiple mechanisms. Perhaps the most well known mechanism is myocardial ischemia precipitated by catecholamine-induced vasoconstriction.18 However, cocaine also has a more direct proarrhythmic effect by interaction with both cardiac sodium and potassium channels.18,19 Cocaine blocks the sodium channel and thus prolongs rapid depolarization, phase 0 of the action potential. Similar to class I antiarrhythmic medications, by prolonging the action potential there is a risk for perpetuating reentry, as it is less likely to encounter refractory myocardium.18 Cocaine is also frequently used in conjunction with alcohol. In this setting a compound, cocaethylene, is formed which also functions to block sodium channels. Thus the arrhythmogenesis of cocaine may be enhanced when combined with alcohol.18,19 The effects on the sodium channels also exhibit use dependence, and thus faster heart rates result in more potent blockade and further slowing of depolarization.19 Given that cocaine increases circulating catecholamines and thus increases heart rate, it potentiates its own effects, thus increasing the risk for life-threatening arrhythmias.18 Not only does cocaine block sodium channels, it also blocks potassium channels responsible for the rapid phase of the delayed rectified current, IKr.18,19 Interestingly, its effects of repolarization are biphasic. At low concentration, it appears to selectively inhibit IKr, resulting in QT prolongation. However, at high concentrations it not only inhibits IKr, but also the inward sodium flow and possibly inward calcium movement resulting in a decrease in repolarization time. As a result, at low doses, one may expect to see more torsades de pointes, owing to IKr inhibition. While at higher doses, slow monomorphic VT may occur due to sodium channel blockade.18


Perhaps the most well-known cause of sudden cardiac death is that of myocardial ischemia and infarction. However, the overall incidence of sustained ventricular arrhythmias, VT or VF, still remains low. In a population of just over 40 000 ST-segment elevation myocardial infarction patients, sustained VT/VF occurred in just 10.2%, with approximately 80% of these occurring within the first 48 hours.20 The frequency of these arrhythmias is even lower in patients with non–ST-segment elevation myocardial infarction (NSTEMI) or unstable angina (UA). In a population of just over 25 000 NSTEMI/UA patients, sustained VT/VF occurred in just 2.1%.21

The pathogenesis behind ischemia causing malignant ventricular arrhythmias is likely related to changes in the resting cardiac membrane potential as well as disruption of the normal ion currents. In the setting of ischemia, the resting membrane potential of the cardiac myocyte is reduced.3 This reduction in trans-membrane potential is due to efflux of potassium ions. Some of this is attributed to ischemia-induced inhibition of the Na+/K+ cotransporter.22 However, this alone does not explain the extent of potassium loss. With ischemia, the myocyte must switch to anaerobic metabolism, generating anion by-products such as lactate and phosphate, which diffuse out of the cell. Potassium may follow these anions in order to maintain electro-neutrality.23 The results of these changes are reduction in action potential velocity and slowing of conduction time. These areas of slowed conduction, in ischemic tissue, are adjacent to areas of normal conduction, in nonischemic myocardium. This creates an environment where unidirectional block can occur and reentry can be established, and the ultimate result is VT/VF.3


The treatment of reversible sudden cardiac death should be directed to the underlying cause when possible. In the case of electrolyte abnormalities hypo/hyperkalemia, hypomagnesemia, and hypocalcemia should be corrected. In the case of QT-prolonging drugs, these should be discontinued. In these situations when torsades de pointes is likely the malignant arrhythmia, it is imperative that potassium be replaced and intravenous magnesium be administrated. Increasing extracellular potassium helps to increase the rapid component of the delayed rectifier current, IKr and decrease the drug-induced block. This accelerates repolarization, helping to shorten the QT interval. Magnesium does not shorten the QT interval, and its exact mechanism of decreasing arrhythmogenesis is unknown; however, it has been postulated to be related to blocking of calcium channels.16 In cases that are refractory to potassium and magnesium, overdrive pacing at a rate of around 100 bpm may be beneficial by both shortening the QT interval and decreasing the development of early afterdepolarizations.24 When ischemia is the inciting event, focus should be directed on reperfusion therapies.

ICD versus No ICD

Following successful resuscitation from sudden cardiac death, a decision will need to be made regarding the possible implantation of an ICD for secondary prevention. It has been convention that patients, with what was thought to be a transient or reversible cause of cardiac arrest, were at low risk of subsequent death and did not require ICD implantation.1 This appears to be most apparent in the population of patients with an acute ST elevation myocardial infarction as the cause of their sudden cardiac death. In a series that evaluated 143 patients who were successfully resuscitated and then discharged following an out-of-hospital cardiac arrest, patients presenting with ECG evidence of a transmural infarction were at the lowest risk of mortality at follow-up. At 16 months of follow-up no patients in the acute transmural infarction group died, and after 2 years, the group had a mortality rate of 14%. This is compared to the group who had sudden cardiac death not related to an acute transmural MI who had mortality rates of 32% and 43% at 16 months and 2 years, respectively.25 More recent studies have also demonstrated the relative lack of impact on mortality in the setting of recent MI. Two large randomized controlled trials looking at just over 1200 patients who were randomized to ICD versus medical therapy within 40 days of an acute MI with a reduced left ventricular ejection fraction showed no mortality benefit with early prophylactic ICD implantation. While both trials were able to show a reduction in the number of sudden cardiac deaths, this benefit was offset by an increased number of nonsudden cardiac death.26,27

Whereas the data are convincing that patients presenting with sudden cardiac death as a result of acute MI do not benefit from prophylactic ICD implantation, the other potential reversible causes have not been evaluated thoroughly. The Antiarrhythmics Versus Implantable Defibrillators Trial (AVID) clearly showed a benefit of ICD versus antiarrhythmic drug therapy (primarily amiodarone) among patients presenting with VT or VF. However, patients with what were felt to be reversible causes were excluded from the randomized portion of this trial. Yet, a secondary analysis of the nonrandomized registry revealed that at 3 years of follow-up the mortality of this group approached 30%. This was not statistically different from the mortality rate of those patients presenting with primary VT/VF, and when mortality was adjusted for age, ejection fraction, coronary artery disease, coronary artery bypass grafting, and aspirin usage, the mortality in the reversible causes subset was actually greater.28 This illustrates that the determination of patients at low risk is difficult and that patients presenting with what is felt to represent a reversible cause of sudden cardiac death need to be evaluated rigorously and followed closely, given their high mortality rate.


Both of the cases presented at the beginning of the chapter illustrate patients who presented with aborted sudden cardiac death and who had potential causes of their arrest that were reversible. In the case of the young woman, she was being treated with a known QT-prolonging drug, and discontinuation of this drug resulted in normalization of her QT interval. She was also found to have a structurally normal heart, and the presenting arrhythmia was torsades de pointes. She was cautioned to notify her physicians about future use of potential QT-prolonging medications. In this setting she was appropriately deemed to be at low risk for recurrent sudden cardiac death and did not undergo ICD implantation. The second case illustrates a patient with multiple cardiac risk factors who had a cardiac arrest in the setting of mild hypokalemia. He was deemed to be of higher risk for recurrent sudden cardiac death. This determination was made after careful review of his care. While indeed his potassium was low, his presenting sudden cardiac death was not secondary to torsades de pointes, as one would expect with hypokalemia. Also, given his reduced ejection fraction and that he requires chronic diuretic usage for heart failure symptoms, he was felt to be at high risk for recurrent VT/VF, and thus an ICD was implanted. In retrospect, this was the appropriate decision given that at follow-up he was noted to have several pace-terminated episodes of VT.


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