Spontaneous Circulation focuses on advanced ECG interpretation, cardiac pharmacology, hemodynamic assessment and resuscitation, and managing acute coronary syndrome. It is devoted to translating the best evidence-based treatments from critical care, resuscitation, and trauma for bedside use in the emergency department.
Friday, May 01, 2015
Pacemaker and implantable cardioverter defibrillator development has revolutionized the treatment of many kinds of cardiac diseases. The technology advancements have been tremendous, and once-large external batteries are now replaced by gumstick-sized modules as sophisticated as any computer. Unfortunately, the leads that provide sensing, pacing, and defibrillation represent a vulnerable part of the system, and have short- and long-term failure modes. Failure modes can cause a spectrum of issues from minor annoyances to catastrophic failure and death. Failure usually requires replacement of the generator, leads, or both, which subjects the patient to an additional procedure with its own associated complications.
Failure modes include acute perforation, dislodgement, infection, vein thrombosis, migration, conduction failure, insulation damage, and wire externalization.
Silicone Casing Structural Failure: Insulation failure has been seen in several lead designs. The silicone casing around transvenous leads is subjected to conditions that can lead to fracture and structural failure. The proximal length undergoes high muscular stress from the pectoral muscles. It can also be crushed because it’s above the bony thorax wall, causing lead-to-lead or lead-to-can disruption. The distal segment experiences high intracardiac forces and dynamic flexing. There are also fatigue initiation points where the shocking coil is attached to the silicone. The most common site of failure is just below the tricuspid valve. The failure rate is higher in lead designs with dual shocking coils, which has contributed to recommendations against their use. (Figure 1.)
Figure 1. Structural failure of the pacemaker/ICD lead silicone casing and externalized conductors.
The defibrillation or sensing wires can be externalized when the insulin fails. The externalized conductors remain electrically silent and no detectable electrical abnormalities may be seen if their ETFE coating remains intact. The coating, however, is not designed to withstand the intravascular or intracardiac environment, and often becomes damaged quickly and leads to electrical short circuits.
Asymmetric Lead Design: This problem was faced by St. Jude Medical with their Riata silicone-insulated leads, and led to a physician advisory by the Food & Drug Administration. The cross-section of a typical asymmetrical lead design (Riata family) is shown in Figure 2.
Figure 2. Schematic cross-section of a pacemaker/ICD lead. Asymmetric design with redundant defibrillation and sensing wires.
A silicone casing forms the main structural component of the lead. The shocking coil rests on the outside of silicone, and four chambers are within the silicone. Redundant conductors carry the sensing and dual defibrillation wires in three distributed compression chambers. A central axis chamber facilitates the use of a stylet during insertion, and is surrounded by the central pacing multifilar conductor.
Detecting Lead Structural Failure: Silicone structural failure usually occurs four to five years after implantation, and is diagnosed in asymptomatic patients undergoing routine imaging or more commonly after changes in electrical conduction are discovered during interrogation of malfunctioning devices.
Fluoroscopy has demonstrated to have positive and negative predictive value of 88 percent and 99 percent, respectively, and is the gold standard method for detecting lead failure. (http://bit.ly/1BokSBa.) Small studies have suggested that chest radiography may be an adequate screening tool, but this has not been widely adopted. Echocardiography cannot reliably visualize a structurally failed lead or externalized conductors, but should be able to demonstrate any intracardiac thrombus that has formed. (Figure 3.)
Complications of Structural Lead Failure: Besides electrical failure, the externalized conductors are highly thrombogenic and can cause thrombus formation. Usually, this can be treated with systemic anticoagulation, though the extent of the clot and secondary effects, such as SVC syndrome, may require explanation of the leads.
Unfortunately, for patients who have these leads implanted, there are no current recommendations for screening intervals or long-term follow-up. Routine removal of the leads is not recommended. If a thrombus formation does occur, systemic anticoagulation should be pursued before surgical or transvenous removal of the leads, which can be difficult and has a high complication rate.
Figure 3. Fluoroscopy image (schematic) of failed pacemaker/ICD lead with externalized wire.
Tuesday, March 31, 2015
Ancient societies figured out that hypothermia was useful for hemorrhage control, but it was Hippocrates who realized that body heat could be a diagnostic tool. He caked his patients in mud, deducing that warmer areas dried first.
Typhoid fever, the plague of Athens in 400 BC and the demise of the Jamestown Colony in the early 1600s, led Robert Boyle to attempt to cure it around 1650 by dunking patients in ice-cold brine. This is likely the first application of therapeutic hypothermia, but it failed to lower the 30 to 40 percent mortality rate. One hundred years later, James Currie tried to treat fevers by applying hot, cold, and warm to the surface and having the patients drink liquids at those temperatures. These innovations were not any more successful than the brine, however.
Hydropaths, popular in the early 1800s, were referred to by Sir William Osler as “hermaphrodite practitioners who look upon water as a cure-all.” He realized, however, the therapeutic effects of using water for compresses and baths. One hydropath taught Osler that a rigid protocol of cold baths for typhoid fever could save lives, and Osler implemented this at Johns Hopkins. He published this protocol in the article, “The Cold-Bath Treatment of Typhoid Fever” in 1892, and physicians everywhere saw a drop in mortality.
Physicians had come to believe by the 1930s that cold was incompatible with life. All clinical thermometers of the time were calibrated only to 94°F, and this thermal barrier was so deeply ingrained in medical techniques that subnormal temperatures were combatted at all costs. Electrical heating devices or hot water bottles and warm blankets were considered necessary emergency equipment in every hospital, but this was about to change.
Therapeutic hypothermia’s father was Temple Fay, MD, a neurosurgeon at Temple University. As a medical student, he was unable to come up with a response when his mentor asked why tumors were less common in the extremities. This ultimately led him to experimental cancer study. He published work in 1937 on how hypothermia suspended cancer cell growth but normal temperatures allowed their growth to resume.
He treated his first patient with hypothermia in 1938 to prevent cancer cells from multiplying. Chloral hydrate and sodium bromide (sedatives) were given by rectum the night before. Paraldehyde, another sedative, was given immediately before hypothermia induction. The patient was cooled to 32°C for 24 hours.
He described it like this: “The first attempt at general refrigeration was made on November 28, 1938…. I … shut off the heat … and opened the windows [to aid] the cracked ice. … For many reasons, chiefly because of the prejudice on the part of the nurses, we had not dared submerge the entire patient in a bed of cracked ice. … The nurses’ home, interns’ quarters, and [other services] were alive with dubious comment….”
A series of patients were treated, but the nurses detested working on the “refrigeration service,” as they called it. “Frankly, the nurses were scared. They could not get the patients’ temperature with the clinical thermometers. The long-stem laboratory thermometers might break in getting a rectal reading. The ice and ice water were always in the way, even when the patient was turned. The pulse was weak. The breathing was shallow. They couldn’t get the patient’s blood pressure. … The entire project of general refrigeration had snowballed into a vast issue of distortions of truth, and even my friendly colleagues began to look askance, and asked how long this absurd experiment was going to be permitted.”
The program was almost shut down, but Dr. Fay and the hospital engineers made blankets from rubber tubes to carry a cold solution from a special “beer cooler.” Commercially available machine pumps were found useful in this technique, and they also developed electric thermocouples for 24-hour charting of rectal temperatures.
“What we learned after breaking the human thermal barrier on the hypothermic side was that human survival was possible under proper supervision. When total body refrigeration was established above 24℃, that hypothermic state could be maintained for 10 days (probably longer if required) when temperature levels of 29.4-32.3℃ were maintained,” he wrote. Dr. Fay also developed refrigeration techniques to reduce pain, and in 1945, was first to publish on using hypothermia for cerebral trauma.
During World War II, Germans confiscated one of Dr. Fay’s manuscripts that had been sent to Belgium for publication. German pilots downed in frigid waters would succumb to freezing temperatures, even if rescued quickly. This led to hypothermia recovery experiments on concentration camp victims in one of the most grotesque, unethical distortions of medicine ever. When the German atrocities were discovered, it set back the field by 10 years, but by the 1950s, research in hypothermia expanded and great strides were made.
Bigelow, et al. quickly perfected general hypothermia for intracardiac surgery in 1950, benefiting the brain and the heart. (Ann Surg. 1950;132:849.) Rosomoff and Holaday worked out much of the physiology in 1954, figuring out that therapeutic hypothermia reduced cerebral oxygen consumption, blood flow, and metabolic rate, demonstrating a direct effect between body temperature, intracranial pressure, and brain volume. (Am J Physiol 1954;179:85.)
Niazi and Lewis found in the late 1950s that patients’ temperatures could be lowered to even 9°C and then rewarmed with complete recovery. This would help patients with accidental hypothermia.
Some 20 years later, a landmark paper by G. Rainey Williams, Jr., MD, and Frank Spencer, MD, from Johns Hopkins reviewed four cases where it was used in cardiac arrest. (Ann Surg 1958;148:462; http://1.usa.gov/1BvriDi.) This is an absolutely fascinating report of patients who suffered cardiac arrest, received open chest cardiac massage to achieve return of spontaneous circulation, and were treated with hypothermia. It had some early success, but severe complications overwhelmed the benefits as its use became more widespread. Cardiac irritability and ventricular fibrillation when patients’ temperatures were below 30°C were problems because precisely meeting a target temperature with the available equipment was nearly impossible.
Later, in 1959, Williams and Spencer, now joined by Benson and Yates, published “Use of Hypothermia after Cardiac Arrest.” (Anesth Analg 1959;38:423.) Two of 27 patients failed to achieve ROSC; six had no coma and were excluded from analysis. Twelve of the remaining 19 received hypothermia; seven did not. One of the seven survived in the untreated group, and six of 12 survived in the hypothermia group (14% vs 50%). They treated the patients at 30-32°C from 34 to 84 hours, and stopped based on the patient’s response. By 1959, induced hypothermia was also used for cardiac surgery and by neurosurgeons for head and spinal cord injuries.
Severe complications became apparent as therapeutic hypothermia became more widespread. Cardiac irritability and ventricular fibrillation when patients’ temperatures were below 30°C became problematic because it was nearly impossible to precisely meet a target temperature with the available equipment. There also was a much higher rate of infections, most significantly a decreased clearance rate of staphylococcal bacteremia, and vasospasm, increased plasma viscosity, hyperglycemia, cardiac dysfunction, and coagulopathies. These complications made its use risky and difficult to manage without intensive care, and the technique was essentially abandoned.
The few human papers on therapeutic hypothermia published after this time reinforced hypothermia’s problems. Bohn, et al. published a case series in 1986 of 24 children who remained in persistent coma after being resuscitated from drowning. (Crit Care Med 1986;14:529.) They used therapeutic hypothermia to treat elevated intracranial pressure; those treated had a much higher rate of neutropenia and septicemia than the control group.
Cardiac arrest care, however, advanced during this period. Zoll published a study about counter shocks for ventricular fibrillation (N Engl J Med 1956;254:727), and Kouwenhoven (JAMA 1960;173:1064) and Safar (Anesth Analg 1961;40:609) introduced closed chest massage in 1960. The 1970s and 1980s saw cardiac arrest care systems developed such as defibrillators in 1979. “Accidental Death and Disability: The Neglected Disease of Modern Society” in 1966 by the National Academy of Sciences spurred the development of EMS systems across the country. (http://bit.ly/1BC5XZG.) Richard Cummins, MD; Joseph Ornato, MD; William Thies, PhD; and Paul Pepe, MD published their “chain of survival” concept in 1991. (Circulation 1991;83:1832.) CPR and defibrillators were now available outside the hospital and in the field, and widespread early resuscitation from cardiac arrest became a reality.
Disappointment set in again, though. Patients continued to do poorly despite improvements in cardiac arrest care. Only a tiny fraction was surviving, and they suffered profound neurologic sequelae. Becker, et al. summed up the frustration with the paper, “Outcome of CPR in a Large Metropolitan Area — Where Are the Survivors?” in the Annals of Emergency Medicine. (1991;20:355.)
Sterz, et al. published a 1991 animal study showing mild hypothermia initiated immediately after ROSC improved neurologic outcomes. (Crit Care Med 1991;19:379) The target of 34-36°C temperature target was unique and several degrees warmer than much of the earlier literature. More than that, they maintained the target temperature only for one hour post-resuscitation, and then let the temperature climb passively. Therapeutic hypothermia was back in fashion.
Bernard, et al. from Monash Medical Centre in Australia published the paper, “Clinical trial of Induced Hypothermia in Comatose Survivors of Out-of-Hospital Cardiac Arrest,” in Annals of Emergency Medicine in 1997. The pilot study prospectively followed 22 comatose resuscitated patients treated at 33°C for 12 hours, and compared them with 22 retrospectively matched controls. Mortality was 10 vs 17, and CPC 1 or 2 was 11 vs 3.
Bernard and his colleagues expanded on their paper in 2002 in the New England Journal of Medicine article, “Treatment of Comatose Survivors of Out-of-Hospital Cardiac Arrest with Induced Hypothermia.” (N Engl J Med 2002;346:557.) They prospectively randomized 77 patients with resuscitated VF with persistent coma. They excluded pregnancy and persistent cardiogenic shock despite epinephrine. All received lidocaine. The MAPs were maintained between 90-100 mm Hg, pO2 > 100, and pCO2 of 40. Patients were cooled to 33°C for 12 hours before being allowed to rewarm passively. Mortality was similar in both groups, but patients with CPC 1 or 2 were 21 vs 9 if they had been treated with hypothermia.
Another study, “Mild Therapeutic Hypothermia to Improve the Neurologic Outcome after Cardiac Arrest,” enrolled 237 patients with resuscitated ventricular fibrillation arrest treated with therapeutic hypothermia to 32-34°C for 24 hours and compared them with normothermic patients. Median time to starting cooling was 105 minutes post-arrest, but the patients did not reach target temperature until nearly eight hours after the arrest. There was a 14 percent absolute risk reduction in mortality and a 16 percent improvement in CPC 1 and 2 scores for patients treated with hypothermia.
Hypothermia was then endorsed by the American Heart Association in 2002 and by the Advance Life Support Task Force of the International Liaison Committee on Resuscitation in 2003. Its use in post-resuscitation care spread widely and quickly as a standard of care. But other controversies developed as the practice became more widespread. Treatment was expanded to resuscitated rhythms other than the ventricular fibrillation and ventricular tachycardia under the assumption that brain ischemia from any source would benefit from hypothermia. Guidelines had adopted 32-24°C, but the optimal temperature target was uncertain.
Work at the Safar Center for Resuscitation in Pittsburgh led to the paper by Logue and Callaway, “Comparison of the Effects of Hypothermia at 33°C or 35°C after Cardiac Arrest in Rats.” They were able to demonstrate that minimal hypothermia at 35°C was as good as cooling to 33°C in mortality and neurologic outcomes, and both were better than normothermia. (Acad Emerg Med 2007;14:293.)
Zeiner, et al. published data that a fever in the post-cardiac arrest period had adverse neurologic outcomes, so researchers postulated that the neurologic benefit had little to do with hypothermia and is more the result of preventing hyperthermia. (Arch Intern Med 2001;161:2007.)
Then came a paper by Nielsen, et al. that enrolled 950 patients in 36 centers remained unconscious after being resuscitated from out-of-hospital cardiac arrest. (N Engl J Med 2013;369:2197.) Any initial rhythm was allowed, which is in line with current practice. They were randomized to temperatures of 33°C or 36°C for 28 hours and rewarmed. Normothermia was maintained until 72 hours post-arrest. There was a non-significant two percent mortality difference at the end of the treatment protocol and 180 days later. Patients with a CPC score 3-5 were 54% vs 52%; this was not statistically significant.
Critics, however, said patients in this study had short no-flow times that may not have been valid for a wider population. The study was designed as a non-inferiority study powered to find an 11% absolute risk reduction between 36°C and 33°C, which would be a NNT of 9. That is asking a lot of any cardiac arrest treatment besides chest compressions and defibrillation.
The adoption of higher temperatures is widespread but not complete. The critical care involved in maintaining a patient at 33°C compared with 36°C is much larger but not significantly so. The risks and complications are higher but, again, not significantly. Hypothermia seems to convey a mortality and neurologic benefit compared with normothermia, but preventing hyperthermia may be the greatest benefit.
Read more about therapeutic hypothermia in our archive.
Monday, March 02, 2015
The vagaries of any list or group are that invariably some members are far more popular than others. Hyperkalemia gets all of the attention when we talk about the cardiac effects of electrolyte abnormalities. It is certainly important (read: life-threatening), and we have multiple life-saving treatments that lend themselves well to testing.
We are well versed in hyperkalemia, though one of its treatments has become controversial (I am looking at you, kayexalate). But other electrolyte abnormalities beyond hyperkalemia also deserve attention.
Hypokalemia: The potassium level in the body is closely regulated, but hypokalemia can still develop by several mechanisms, including gastrointestinal loss, renal potassium wasting, or shifting potassium into the intracellular space with an alkalosis. Characteristic changes in the ECG are associated with hypokalemia, which become more prominent as the hypokalemia worsens. The T waves flatten, and may disappear. A U wave may develop, seen as a small deflection after the T wave and in the same direction. Its magnitude is usually <0.5 mm, but it is inversely proportional to the pulse, becoming larger at a slower heart rate. It is most prominent in V2 and V3. It is important not to mistake the QU interval for a prolonged QT interval.
ECG of patient with hypokalemia and hypomagnesemia.
The myocardium is very sensitive to hypokalemia, with its largest effect on inhibiting the action of the delayed rectifier potassium channels (IKr) reducing the outward potassium current. Even though the cardiac action potential is prolonged, the refractory period remains unchanged, which dramatically increases the chance after depolarizations that can lead to ventricular arrhythmias. These effects may be exacerbated by ischemia or digoxin toxicity. Hypokalemia also increases the hyperpolarization in the AV node, which increases the effects of acetylcholine suppression on AV conduction (negative dromotropic).
Hypomagnesemia: Hypomagnesemia seldom occurs by itself, and is usually associated with hypokalemia and hypocalcemia. Magnesium is an important cofactor for ATP pumps as is found in the renal tubule responsible for potassium reabsorption, which is why hypomagnesemia seldom occurs in isolation, and is almost invariably associated with renal potassium loss and hypokalemia. Ninety-five percent of body magnesium is intracellular. Serum magnesium levels are a poor indicator of total body magnesium level, and usually reflect acute events. The multiple electrolyte abnormalities make it difficult to document isolated ECG effects of the low magnesium. Nevertheless, the most common ECG effects are global T wave inversions and prolonged QT interval.
The most significant effects of hypomagnesemia are atrial and ventricular ectopy and dysrhythmias. Magnesium levels affect the release of calcium from the sarcoplasmic reticulum by blocking the L-type calcium channels. Calcium is blocked when magnesium levels are high. Conversely, additional calcium is released into the myocyte cytoplasm at low magnesium levels. This calcium has an important role in excitation contraction coupling of the myocardial cell, which precipitates all manner of arrhythmias. It is difficult to tell, however, if this is a specific effect of the hypomagnesemia or from the concurrent hypokalemia.
Whatever the origin, torsades de pointes and polymorphic ventricular tachycardia in QT interval prolongation respond to magnesium infusion. The magnesium suppression of early afterdepolarization (EAD) occurs by blocking the calcium influx so that the amplitude of EAD is reduced to subthreshold levels.
Hypercalcemia: Half of serum calcium is bound to proteins (mostly albumin), and the remaining unbound (or ionized) calcium produces the physiological effects and ECG changes. The amount of calcium bound to protein varies with acid-base balance. As the blood becomes more alkalemic, the more calcium becomes ionized. Calcium channels act mainly in the phase 2 of the myocardial action potential.
The QT interval is shortened with higher worsening hypercalcemia. The ST segment in severe cases may be shortened so much that it appears absent, and the T wave starts almost at the end of QRS complex. An uncommon finding of hypercalcemia is ST-segment elevation mimicking acute myocardial infarction. Because the QT interval is shortened in hypercalcemia, initial upslope of the T wave, which starts immediately after the QRS complex, mimics the hyperacute phase of acute myocardial infarction.
Severe hypercalcemia can cause appearance of Osborn waves, which are positive deflections occurring at the junction between the QRS complex and the ST-segment. The excess of calcium can also cause ventricular ectopy and irritability, which can lead to malignant arrhythmias and cardiac arrest.
ECG of patient with hypercalcemia and hypokalemia.
Hypocalcemia: Hypocalcemia affects mainly the L-type calcium channel, and prolongs phase 2 of the cardiac action potential. This can be seen in the ECG as a prolongation of the ST-segment. Calcium channels close at the end of phase 2. The T wave from phase 3 repolarization is mostly related to potassium channel activity, and it is not significantly affected by calcium levels. ST-elevation mimicking myocardial infarction can be seen in cases of severe hypocalcemia.
ECG of patient with hypocalcemia and hypokalemia. U waves are demonstrated as are prolonged ST-segment and QT intervals.
Hypocalcemia is often associated with other derangements, which obscure the ECG findings, as with electrolyte abnormalities. Renal failure, for example, can often produce hyperkalemia and hypocalcemia. Treating these patients with calcium replacement can be especially beneficial because it not only reduces the myocardial irritability of hyperkalemia but also treats the hypocalcemia.
Monday, February 02, 2015
We physicians are obsessed with classifying, sorting, and differentiating in a quest for never-ending precision. We gather all manner of “facts” from our patients. Sights, smells, reactions to pushing or pulling. We divine sounds with antiquated stethoscopes or peer underneath the skin with ultrasound. We subject them to tests of blood, urine, and fluids from any place our needles can reach.
All of this is to arrive at an exact diagnosis that is often frustrated by the secondary nature of the data. Our disappointment has driven us mad, but the promise of exactness from biomarkers leaves us giddy. We have convinced ourselves that these laboratory tests will provide us the dichotomous yes/no answers we tell ourselves that our patients demand, but is really more for us. Answers without all of the messiness.
Does the patient have pneumonia? Check procalcitonin. Want to know if he has a pulmonary embolism? How high is the D-dimer? Why is the patient short of breath? Better get a BNP level. Chest pain? Run a troponin level (three times every four hours).
Troponins have turned on us, however, and emergency physicians and cardiologists are quickly learning to hate their old friend. Troponin levels were such a good biomarker. Positive levels were a clear marker of acute myocardial infarction; negative values ruled out the diagnosis. Exactly what we wanted from a biomarker. As the clinical chemists devised ways to measure troponins at lower and lower levels, however, we started to find patients with positive troponin levels who were not having acute coronary syndrome (ACS). Deciphering the meaning of a positive troponin is becoming less clear, making our lives messy again.
Troponin is found as a complex (troponin I, troponin C, troponin T) in myocardial cells that displaces tropomyosin when activated by entering calcium, exposing binding sites on actin for myosin. In short, troponin forms the trigger mechanism that starts heart cells contracting, two fortunate facts that make it useful as a marker. First, there is a version of troponin I and T that are only present in myocytes. Second is that the cardiac form of troponin is about 50 percent different from the skeletal muscle version. These two facts together mean that we can specifically measure the cardiac version, and that any way we measure we know is coming from the heart, not skeletal muscle.
Intracellular troponin is mostly bound as a complex (94%) attached to tropomyosin with only 6% free in the cytosol. It must be released from the cell for us to measure troponin levels in the blood. This has traditionally been assumed only to occur when cells die and leak their contents, but several alternative mechanisms are likely. First, there is natural turnover of myocardial cells. About 40 percent of all myocytes will turn over (programmed cell death can occur as apoptosis or autophagy) during a person’s life. The troponin proteins wear out, and are degraded by proteasomes within the cell cytoplasm into fragments. These can be released and measured by the assays. Lastly, oxidative stress can increase cell wall permeability or cause formation of cellular blebs, allowing for the release of fragments and free cytosolic troponin. These mechanisms mean that even normal individuals have measurably low troponin levels, which we can now detect as our assays have become more sensitive.
Once troponin is released from the cell, its half-life (t½) is approximately 120 minutes before it is cleared renally. Troponin can continue to be measured for longer periods after an insult because there is continued released from the myofibrillar pool as myocytes continue to undergo degradation during necrosis.
The original troponin assay was developed in 1987. Unlike measurement of CK-MB, an enzymatic assay, troponin is a protein, and assays use a sandwich ELISA method. The capture antibody has binding sites directed at cardiac-specific epitopes on the troponin molecule. The detection antibody binds different epitopes to increase specificity. Determining which epitopes to target is dependent on the manufacturer, but no two antibody pairs can have 100% sensitivity because of their existing troponin fragments, post-translational modifications, oxidation, phosphorylation, and complexes.
So what defines a high-sensitivity test? The important point to remember is that we are talking about analytical sensitivity, not clinical sensitivity. The sensitivity of detecting troponin, not how useful that measurement is, answers our clinical questions, such as whether the patient is having a myocardial infarction. Two criteria have been established for assays to be labelled high-sensitivity. The first is that it must be able to measure a detectable value for 50% of healthy individuals. This is called the limit of detection. The second criterion is coefficient of variation (CV). This is the analytical impression at the 99% percentile. Most contemporary tests are about 20%, and high-sensitives are generally much better. The lower sensitivity is important, but the more precise CV may actually be more clinically useful because it makes troponin measurements easier to repeat, especially at the lower values. Table 1 lists generations of troponin assays, and Figure 1 provides a visualization of the assay criteria.
Manufacturers reengineered the detection antibody to meet the criteria of high-sensitivity assay. They also increase the sample volume, raise the ruthenium concentration, and optimize the buffer to reduce background noise.
A challenge that manufacturers face is defining what constitutes a healthy population and establishing the 99th percentile upper limit normal (ULN). The normal has age and sex variations. Some manufacturers obtain only a health questionnaire (ranging from simple to extensive), while others perform a physical exam, ECG, and echocardiogram. How the healthy population is defined can have significant effects on the normal limits established. There are no guidelines, but current recommendations suggest establishing one cohort of patients under age 30 and another over age 30 with a median age of 60-65. A detailed history should be taken, the blood should be measured, and BNP should be obtained to screen for cardiomyopathy. Of course, patients included should have an equal sex and racial mix. At least 400-500 individuals are needed to obtain a statistically valid sample.
Using the high-sensitivity assays in healthy populations, we have started to notice significant biologic variability. That is variation of troponin levels over a day and other cycles, which may become important when assessing serial measurements as part of evaluations.
After all of this work developing a more advanced troponin assay, we are at least left with something very useful. Well, maybe. Before we can answer the clinical usefulness of high-sensitivity troponins (PPV of hs-cTn measurements), we need to understand the definitions and mechanisms of myocardial injury and infarction. Myocardial injury involves cell death, and is indicated by positive troponins. Many mechanisms can cause cell death, however. The myocardial cells become ischemic if they are deprived of adequate oxygen supply, and an infarction can develop if that persists long enough.
But as we know, the clinical presentation of myocardial infarction can vary tremendously, and arriving at a diagnosis can be challenging. A consensus conference has determined diagnostic criteria for myocardial infarction. In the most recent version from 2007, there must be evidence of positive troponins that have a rise/fall pattern indicating acute process with at least one value above the 99th percentile ULN. This must be supported by the appropriate clinical context and either ECG, imaging, or angiography evidence.
Myocardial infarction can be subdivided into subtypes. Type 1 is what we typically think of with the term myocardial infarction — plaque rupture and formation of an intracoronary thrombus. This is an acute coronary syndrome. Type 2 myocardial infarction occurs when there is a temporary imbalance between the perfusion and cardiac oxygen demand. This leads to ischemia and can cause an infarction and necrosis without a plaque rupture or thrombus formation. By definition, this is not an acute coronary syndrome despite the presence of elevated troponins, so it is important to note that myocardial infarction is not synonymous with ACS. Types 3, 4, and 5 are less useful for emergency physicians.
Elevated troponins can also occur because of nonischemic mechanisms that cause direct myocardial damage. The troponins indicate cell death with necrosis, but ischemia was not the mechanism. Examples include cardiac contusion, myocarditis, malignancy, and sepsis.
Unfortunately, distinguishing between type 1 MI, type 2 MI, and nonischemic myocardial injury can be challenging, especially in coronary artery disease. Troponins were found to be more sensitive than CK-MB in those found to have myocardial necrosis, and there is a level-dependent increasing risk for adverse outcomes. The elevation itself, however, does not provide any information about etiology. It does indicate myocardial injury, but it fails as an absolute biomarker for acute myocardial infarction. Clinical context is very important, and the entirety of the clinical presentation (history, physical exam, ECG, imaging, and angiography) matters in determining the diagnosis. The dynamic rise and fall of troponins on serial measurement can help establish that there has been an acute myocardial injury, rather than a baseline troponin elevation as may be seen in renal failure. A diagnosis of type 2 MI should be considered only when there is clinical evidence of an acute imbalance. Nonischemic mechanisms should be evident from the history. Ultimately in cases where the diagnosis remains uncertain, advanced imaging such as cardiac MRI may be useful.
Tuesday, December 09, 2014
Nursing home staff became concerned about a patient because he was “floppy.” He was a 59-year-old man with stage 3 chronic kidney disease, right ventricular heart failure, hypertension, cirrhosis, and insulin-dependent type 2 diabetes mellitus. He had been sleeping all day, according to his nurse, but he was not responding when she checked on him in the evening, and she could “drop his arm and it would just hit his face.”
He was hypotensive (90/50 mm Hg) and bradycardic (about 30 beats/min) in the ED. Respirations were slow and shallow. He was protecting his airway, but was hypoxic (SpO2 82%). IV access was established, and initial laboratory tests were sent. He was orotracheally intubated without difficulty and easily ventilated. Atropine was given, but did not increase his heart rate. The symptomatic bradycardia meant starting transcutaneous pacing. Fingerstick glucose was 174 mg/dL. Given his history of kidney disease and diabetes mellitus, there was a high suspicion for hyperkalemia so he was empirically treated with calcium gluconate and shifted with insulin/glucose. It was difficult to get good electrical capture with the transcutaneous pacing. Multiple different pad locations were attempted, and eventually we were able to achieve intermittent capture using pads in the right-parasternal and apex position.
A 12-lead ECG was obtained that demonstrated sinus bradycardia with a narrow QRS complex and no T-wave abnormalities. (Figure1.) There was no ST-segment changes concerning for ischemia.
Figure 1. Presenting ECG with initiation of transcutaneous pacing. The large voltages recorded on the right side of the ECG occurred when the transcutaneous pacing was started.
A limited transthoracic echocardiogram showed severe bradycardia in action, but the actual contractility was normal, and no focal wall motion abnormalities were identified. (Figure 2.)
Figure 2. Click here to see a limited transthoracic echocardiogram using the subcostal window.
A small pericardial effusion could be seen as the thin hypoechoic line starting anteriorly and wrapping around the apex to the posterior aspect. No echocardiographic evidence for tamponade was present based on the lack of right ventricle collapse during diastole.
Abdominal ultrasound was notable for a small amount of intraperitoneal free fluid, pleural effusions, and a dilated IVC with no respiratory variation. (Figures 3, 4, and 5.)
Figure 3 (left). Abdominal ultrasound in the hepatorenal (Morrison) window. A small amount of free fluid is visible in the potential space between the liver and kidney. Figure 4 (center). Right thoracic ultrasound showing pleural effusion. Lung parenchyma is usually anechoic, preventing visualization of the posterior lung bases. The lung base is clearly seen in this situation, however, and is hypoechoic, indicating a fluid-filled area consistent with pleural effusion. Figure 5 (right). Ultrasound view of the IVC. It is dilated, and there was no respiration variation. Click here to watch an ultrasound of this finding.
This was presumed to be volume overload from a combination of ascites given the patient’s history of cirrhosis and renal failure.
Initial laboratory tests showed normal blood counts and a chemistry panel that was notable for a potassium of 7.4 mEq/dl. Given the difficulty of achieving adequate transcutaneous pacing, a right internal jugular introducer sheath was inserted, and a transvenous pacing wire was placed with successful mechanical and electrical capture. (See Table 1 for how to place a transvenous pacemaker. Figure 6 shows the pacing wire within the right ventricle.)
Table 1. Abbreviated Procedural Steps for Transvenous Cardiac Pacing
1. The entire procedure should be done under sterile conditions with full barrier drapes.
2. The sterile sleeve should be placed on the pacer wire once the sheath introducer is placed.
3. Inflation of the floating balloon should be verified.
4. The proximal (+) lead should be on the positive terminal on the connector adaptor.
5. The distal (-) lead should be attached to lead V1 on the cardiac monitor using an alligator clip.
6. The balloon should be inflated after the pacing wire is threaded 15-20 cm to exit the end of the sheath.
7. Advance the pacing wire in a smooth fashion while monitoring the ECG. Marked ST-segment elevation will occur when the lead tip contacts the endocardium.
8. Secure the protective sleeve.
9. Detach the negative lead from the ECG, and connect it to the connector adaptor of the pulse generator.
10. Initial generator settings should be 80 beats/min, output 5mA, and sensitivity of 3 mV.
11. You should be able to note mechanical capture by noting cardiac contractility at the rate set on the pulse generator. This can be done by palpating a pulse or contractions over the anterior chest wall or by visualization using ultrasound.
12. Test electrical capture by challenging the required output threshold and sensitivity.
A. With sensitivity set to maximum, gradually reduce your output threshold until electrical capture is lost. Set the output threshold at 2-2.5 times the value at which capture was lost.
B. Set the rate at 10 beats/min above the intrinsic rhythm. Place the pacemaker in asynchronous mode and ensure complete capture.
C. Then with the sensitivity set at about 3 mA, decrease the rate until pacing ceases. Verify that the generator is indicating that a native beat is sensed on every cycle. If not, increase the sensitivity. Reduce the sensitivity if the pacer oversenses and is being triggered by p or T waves. Set the sensing level at half of the value once the sensing level is determined (i.e., reduce the sensitivity by half.)
Figure 6. Click here to see a cardiac ultrasound in subcostal window. Transvenous pacer wire can be visualized as the hyperechoic structure within the right ventricle.
A chest radiograph and ECG was not obtained in ED following placement of the transvenous pacemaker. The patient was admitted to the medical ICU and cardiology consultation was requested. Emergent hemodialysis was arranged with the nephrology service. Unfortunately, intermittent loss of capture started occurring during transport from the ED to the ICU and from the trolley to the bed. Within a short time, the transvenous pacemaker failed capture completely despite increasing the output and sensitivity settings on the pacemaker, and the patient returned to his native bradycardic rhythm. The admitting team obtained a chest radiograph. (Figure 7.)
Figure 7. AP chest radiograph after arrival in the ICU.
The endotracheal tube is in good position, and external pacer pads are over the left hemithorax. The pacer wire takes a crazy course, however. It can be seen entering from the top of the film through the right internal jugular vein and descending the SVC (right of midline) to the heart. It is coiled in the right ventricle, however, and part of the wire is likely looping through the tricuspid valve. The electrode tip appears to be abutting the high septal wall. A schematic is shown to help visualize the misplaced pacer wire. (Figure 8.)
Figure 8. Schematic of misplaced pacing wire.
A 12-lead ECG was obtained immediately after the pacer was placed. (Figure 9.) Pacer spikes appear prior to each QRS complex. The emergency physician interpreted this ECG as an indication of successful placement, which is why a chest x-ray was not immediately obtained. This is an abnormal ECG for a patient undergoing transvenous pacing, however. The QRS complex is narrow with an axis downward and to the left, indicating that the lead contact is atrial or high on the septal wall. A properly placed right ventricular lead placement in the apex should result in a LBBB and an upwards QRS complex. Capture was likely lost when the pacing tip was pushed out of the ventricle and was not in contact with the right atrium wall.
Figure 9. ECG after transvenous pacer placed.
The patient was taken to the cardiac catheterization lab to reposition the pacing wire under fluoroscopy. The wire was confirmed to be coiled and almost tied in a knot. The tip was in the atria, and the floating balloon was partially inflated. It was repositioned without difficulty and achieved excellent capture. The patient was returned to the MICU, and ultimately underwent emergent dialysis to correct the underlying hyperkalemia.
Cardiac pacing can be a life-saving procedure, and the emergency physician should be ready to place a transvenous pacer if transvenous pacing is unsuccessful. Familiarity, practice, and checklists can dramatically increase the probability of success and enhance patient safety.