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Session I: Basic Science and Fundamentals of Elect ...
Workshop #1: Electrocardiographic/Electrophysiolog ...
Workshop #1: Electrocardiographic/Electrophysiologic Correlations
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Greetings, this is John Miller from Heart Rhythm Society Core Concepts in Electrophysiology. I'm going to have some workshop questions that we'll go over. These are board type questions that one may encounter. These are my disclosures for your viewing pleasure. Here's our first question. The rhythm strip shown above is from a 77-year-old woman two days after hysterectomy. Two seconds after the end of the strip shown, QRS complexes reappeared. She felt lightheaded and thinks she was having a bowel movement at the time. She's never had syncope. Based on this information, you advise dual chamber pacemaker insertion, electrophysiological testing with stressing of the conduction system, continued observation, that is no specific testing or therapy, or a stool softener. You can analyze the strip and come back to us when you're ready. The correct answer is dual chamber pacemaker insertion. Why is this? Well, this is a case of paroxysmal AV block, and it's initiated by a non-conductive P wave you see there. It's not very obvious, but you can see it in both leads. This is not a bagel episode. We do not have lengthening of the PP or PR intervals along here. In fact, we have some shortening of the PP intervals as it goes on. This is not a bagel episode. This is a potentially life-threatening disorder. It is initiated by atrial or ventricular premature complexes. Quite often, it is terminated by another PAC or PVC. Unless that escape valve is pulled by the heart, this may continue, and the patient may have perpetual AV block. The physiology of this is phase four depolarization within a somewhat diseased hysperkinesis system that shouldn't be doing this. It's almost a threshold, and it gets some channels activated, but not enough to generate a regenerative action potential. Then an incoming beat comes and finds the cell not stimulatable, the group of cells not stimulatable. The cycle just repeats, and the conduction system remains in perpetual refractoriness. Unless something comes along to make a perturbation and interrupt this cycle, the individual may die. Pacing is definitely an indicator for this. Nothing that you will learn from EP study will give you any more information. This is not a reliably provocable event. Anything you'd learn, if it were provocable at EP study, you'd say, okay, the patient needs a pacemaker. They need a pacemaker anyway. This is not a bagel event. This is not something to be dismissed. The stool softener is not going to solve this problem, and no matter what, there's... Continued observation is, oh, she'll probably be all right. It's only happened once. Now this is her chance. This is your chance to help this lady survive. Next question. A 57-year-old man is undergoing electrophysiologic study for evaluation of syncope. Tracing that I will show shows the following possibilities. Anterograde right bundle branch block and retrograde left bundle branch block, anterograde right bundle branch block and retrograde his bundle block, bidirectional right bundle branch block and retrograde AV nodal block, bidirectional right bundle branch block and retrograde his bundle block, or bidirectional right bundle branch block and retrograde gap phenomenon. Okay, here's the trace. And you can go back and forth on this and cogitate as long as you want and rejoin me when you're ready. I'm ready. The answer is bidirectional right bundle branch block and retrograde AV nodal block. Why is that? Well, if you look here, we have an anterograde his potential during conduction that has right bundle branch block. So at least we have anterograde right bundle branch block. That his potential occurs after the local ventricular electrogram during ventricular pacing. Here it is here. Here it is here. This is slow pacing. This is not premature pacing. So that suggests that whereas you should see his potential before the local ventricular electrogram if you're pacing the right ventricle, which this is, right RV for pacing, should see a his potential here. The fact that you don't means we have a retrograde right bundle branch block. It goes across the septum and up the left bundle to conducted his. So this is not retrograde left bundle branch block. It's retrograde right bundle branch block. How about AV nodal block? Well, we have a his and we have what looks like a retrograde P wave here, but not here. So there is anterograde and retrograde right bundle branch block demonstrated here, as well as AV nodal block. It's a little tricky, but again, there's one best answer here. And that is the one that is given. So RVBB is present on the surface CCG, his deflection occurring so far after the stimulus artifact indicates right bundle branch block in the retrograde direction as well. You see retrograde his all the time, so it's not retrograde his block and conduction fails on the second beat of the AV nodal. A lot of information. Okay. Question number three. A 63-year-old man undergoes EP study for evaluation of recurrent syncope. Ventricular pacing is performed and based on the recordings, you conclude that retrograde conduction is present over the AV node. Retrograde conduction is present over a right lateral accessory pathway. Retrograde conduction is absent and block is in the his Purkinje system. Retrograde conduction is absent, the block is a navy node or retrograde conduction is absent, but you can't block side of block is indeterminate. Here's the tracer. All right. You can think about that and mull over your choices and come back to me when you are, have your answer. Correct answer is that retrograde conduction is absent and block is in the his Purkinje system. Okay. So let's look at this here. Here we have ventricular capture on each of six complexes that are stimulated. It looks the same each time. We have regular A's along the way here. The A's are all perfectly regular, no relationship to the V's. And it looks, when you can see it, it looks like a sinus P wave. It has a sinus activation and the his and proximal distal CS. So this is a sinus rhythm with ventricular pacing and no VA conduction. Great. Okay. So retrograde conduction is blocked and there is the three choices. Where is the block? It's either in the AV node, which it is in 99.9% of cases, or it's in the his Purkinje system, or you can't tell. I'm going to get rid of the third one. You can tell. If you have block in the AV node, you have concealment into the AV nodes. The AH interval will be prolonged where it has been concealed into. The AH interval is the same on all of these. Therefore, we didn't get into the AV node. Therefore, block was before the AV node. Therefore, it's in the his Purkinje system. The atrial activity is just walking through here during constant rate ventricular pacing, and there is no retrograde conduction. A prolongation gives the clue here as to whether there is penetration into, but not through, the AV node. You have block somewhere. It's usually in the AV node, 99.9% of the cases, it's AV node. This is one case where it is in the his Purkinje system, very diseased. The HV interval is quite long. You can imagine that because this is not answered by a QRS complex here. This is a long HV. It's probably 100, 30, 140 milliseconds. This person did have AV conduction, but it was a very long HV interval, very diseased his Purkinje system. That's why there was block in the his Purkinje system, not getting back to the AV node. There's that AH being the same there. Question number four. A 43-year-old woman has an event monitor for investigation of heart skipping. Based on the findings in the tracing I'll show, you should implant a dual chamber pacemaker, perform EP study and catheter ablation for atrial ectopy, implant an internal loop monitor, or reassure the patient. Here's the tracing. And you can look through this and review your choices and come back when you're ready with your answer. The correct answer is reassure the patient. Why? There's some scary things going on on this tracing here. There's a non-conducted P wave. It looks like Mobitz 2 here. And here's an inverted P wave. It looks weird. Again, not connected. Okay. What's going on here is that sinus rhythm is present almost throughout here. You can march out where P wave should be. There's even one kind of deforming here. Another one kind of deforming there, here, here, obviously. And this is the only P wave that is not sinus. The rest of these are sinus P waves. All right. There are some premature narrow complexes. I think I have arrows. There's that, the interesting ones. But these premature narrow complexes are not caused by a P wave. The P wave is at the red dot. So what are these? If there's a narrow QRS complex that looks like the conducted complex, but a P wave doesn't precede them. It's a junctional P and extra systole. And here they are manifest extra systoles. And these two instances, there are other instances where there are a concealed extra systoles. With this first non-conductive P wave, if you had a HISS extra systole firing right there, it could cause this P wave to not conduct, but it's too early to conduct itself integrally. So blocks below the HISS gets to the AV node, penetrates it, and renders it refractory. So you have apparent Mobitz II block, a P wave that's not conducted in the setting of normal PR intervals. The real trick is this bead over here. This green dot over here indicates an inverted P wave, which is the result of a HISS extra systole that conducts retrogradely, but doesn't conduct integrally. So these are concealed extra systoles having an effect on the rhythm here and here and manifest extra systoles shown here and here. So this is a case where you have four HISS extra systoles on this tracing here, two of them seeming to create AV block, and two of them looking like PACs, except that the P waves march out. So there's no indication for pacing here. There's no indication for EP study or ablation of atrial ectopy, because there's really no atrial ectopy seen on here. And there's no indication for more monitoring within the plant bowl loop recorder. We got everything here. That is the answer. And here's a ladder diagram showing where a HISS extra systole might occur. The A is coming down here trying to penetrate the AV node, but the extra systole occurs here, gets up to the AV node, and conceals into it, preventing conduction. This is the rest of the HISS protingent system is refractory, so it blocks both HISS. In this case, we have the HISS extra systole occurring with slightly different timing. What was so different about it? I don't know, but it conducts to the ventricle and collides with the sinus beat here. Nothing else happens. Same thing here. And here we have an even earlier HISS extra systole that blocks going anterogradely, but is early enough that it gets back to the atrium causes an inverted P wave. So there you have it manifest and concealed his extra systole. So the theme of this workshop was conduction system, abnormal impulse formation and conduction, and how to figure out what's going on there. Thank you very much for your attention. My name is Dr. Barry London. I'm the director of the division of cardiovascular medicine and the director of the Abboud Cardiovascular Research Center at the University of Iowa Carver College of Medicine in Iowa City, Iowa. Today's topic is workshop number one, basic science and channelopathies. And we're going to go through 11 questions. I have no disclosures. The first case, CV is a 54 year old man with a history of long QT syndrome. The, his records report a QT interval of 528 milliseconds with a corrected QT interval of 499 milliseconds. He has no history of palpitations, syncope, neosyncope, and is on no medications. His father was diagnosed when he had a cardiac arrest during chemotherapy. Genetic testing showed a pathological KCNQ1 mutation, the mutation is listed here, in both the patient and his dad. This mutation has been identified previously in multiple patients with long QT syndrome. It co-segregates in a large family with long QT syndrome, and it was identified in a de novo, in a patient with a de novo mutation, meaning that both of his parents were negative for the mutation. EKGs at baseline and during recovery from during an exercise stress test are showed below. So here is baseline electrocardiogram. And here is electrocardiogram three minutes into the recovery period following a maximal exercise stress test. Which of the following best describes the current case? A, CV has long QT type 2 or LQT2. B, CV does not clinically have long QT syndrome and is an example of incomplete penetrance. C, the exercise test is useful for the diagnosis of long QT syndrome and is most sensitive during early recovery. D, there is no role for NADLOL in the absence of symptoms. So the answer is C, the exercise stress test is useful for the diagnosis of long QT and is most sensitive during the early recovery period after the stress test. So in CV, his QTC prolongs to greater than 600 milliseconds during exercise and early recovery, consistent with long QT syndrome and specifically consistent with long QT type 1. So long QT type 1 is caused by mutations in the KCNQ1 gene, which encodes for the KVLQT1 potassium channel. This is the channel that the current of which shortens the action potential and the QT interval at fast heart rates. So patients with long QT1 typically have relatively normal corrected QTC intervals at slow heart rates, but develop marked QTC prolongation at faster heart rates. And these patients get arrhythmias and sudden death with exercise or with stress, similar to what the patient's father had during chemotherapy. Now he doesn't have long QT type 2, which is caused by mutations in KCNH2 gene or ERG, and there the EKG usually shows marked T wave abnormalities. The exercise stress test is useful for the diagnosis of long QT syndrome, especially long QT type 1, and is most sensitive during the early recovery period following exercise when the QT becomes and remains quite prolonged. Natalal, a beta blocker, is highly effective in preventing arrhythmias and sudden death, has been shown to be more effective than other beta blockers, and should be considered for primary prevention. In CV, he was bradycardic at baseline, and although often a beta blocker, he chose not to be on one as he was completely asymptomatic. Second case, genetic testing showed that BM carries a pathologic mutation, mutations listed here, in a splice site of KCNQ1 that is known to cause autosomal dominant long QT type 1. In addition, BM also carries a variant, the variant listed here, in Titan that's been associated with a dilated cardiomyopathy. Further testing included an echocardiogram and a cardiac MRI that were normal. The best diagnosis describing BM are A, long QT1 and non-ischemic cardiomyopathy, B, long QT1 and incomplete penetrance of a Titan mutation, C, incomplete penetrance of a KCNQ1 mutation and non-ischemic cardiomyopathy, and D, incomplete penetrance of both KCNQ1 and Titan mutations. So the right answer is long QT type 1 and incomplete penetrance of a Titan mutation. So BM has long QT syndrome, LQT1 type, because he has the EKG phenotype that is consistent with long QT syndrome. The presence of arrhythmias is no longer required for the diagnosis of long QT syndrome. One only needs QTC prolongation. Now BM also carries a Titan mutation but has normal LV function and no symptoms. He therefore doesn't have a cardiomyopathy and this is an example of incomplete penetrance of the Titan mutation. So he is genotype positive for the mutation but phenotype negative or normal. It would be appropriate to consider initiation of treatment with nadolol for primary prevention of arrhythmias in long QT type 1. Nadolol is extremely effective in preventing arrhythmias, is well tolerated, is more effective than other beta blockers, and might also provide protection for the development of his ischemic cardiomyopathy for which he is at risk because of the Titan mutation. Moving on to case 3. A 47-year-old man with a history relevant for two prior syncopal events comes to you after his 38-year-old brother was resuscitated following a cardiac arrest. His brother was diagnosed with Brugada syndrome and had an ICD placed. The right precordial leads of the patient are shown on tracing 3.1. So this is leads V1 and V2 of the patient whose brother has Brugada syndrome. The next best step is A. Implantation of a defibrillator. B. Genetic testing. C. Reassurance as your patient is beyond the age at which he is at risk for developing Brugada syndrome. D. An intravenous procainamide challenge. And E. EP testing with programmed electrical stimulation looking for inducible ventricular fibrillation. So the best answer here is D. An intravenous procainamide challenge. So in Brugada syndrome, the electrocardiogram is dynamic and provocable. So there are three types of Brugada EKGs. Only type 1, which is a coved ST elevation and T inversions is diagnostic. Type 2 is a saddleback ST elevation with an upright T wave and at least 2 millimeters of ST elevation. And type 3 is the same as type 2 but with less than 2 millimeters of ST elevation. Your patient here has a type 3 Brugada syndrome EKG. So it is saddleback with less than 2 millimeters of ST elevation. This is not specifically diagnostic of Brugada syndrome as this type of EKG pattern is found with a reasonable frequency in the general population. So why the answer that we chose? The indications for a defibrillator in Brugada syndrome are ventricular arrhythmias, symptoms consistent with ventricular arrhythmias, and to some extent a spontaneous type 1 EKG pattern. And he does not have any of those indications. Genetic testing is Brugada syndrome is useful for somebody who definitively has Brugada syndrome. Unfortunately, only about 30% of people will genetically test positive for Brugada syndrome. So it would be appropriate for the patient's brother to be genetically tested for Brugada syndrome. And then if there is a positive gene is identified, then the patient could be tested. That hasn't been done here. Now the age of first presentation of Brugada syndrome is most commonly in the 30s and 40s, but it can happen in older or younger people. And it's no guarantee that your patient won't be diagnosed with Brugada syndrome or have an arrhythmia at some point in the future. The best way to diagnose whether or not he has Brugada syndrome is with a procainamide challenge. So sodium channel block is exacerbate the EKG phenotype of Brugada syndrome, which is largely caused by inadequate inward sodium current. So if he develops a type 1 EKG with the infusion of either procainamide, flecainide, or ajmaline, ajmaline being used in Europe, then that is diagnostic of his having Brugada syndrome. Now patients with Brugada syndrome are more likely to develop inducible ventricular fibrillation when during a programmed electrical stimulation, but that is not useful as a diagnostic test to actually diagnose Brugada syndrome. And there is debate as to whether it helps predict whether people are going to develop symptoms in the future. Case four, a 32-year-old man, Joe, with three children comes to you for evaluation of possible long QT syndrome. His corrected QT interval is 440 milliseconds. His older brother has a corrected QT interval of 490 milliseconds, had aborted sudden death, and has a defibrillator. His pedigree is shown in figure 4.1. So this is figure 4.1. Joe is showed by the arrow. He's 32 years old. His older brother has QT prolongation and has a defibrillator. He is affected. Of interest, Joe's father died suddenly at age 45, and his paternal grandmother died suddenly at age 38, suggesting a familial syndrome. Which of the following statements best describes the role of genetic testing in this family? A, genetic testing will have no benefit clinically in this family. B, Joe should be tested using a long QT gene panel. If positive, others in the family should be tested through cascade screening. C, Joe's brother should be tested using a long QT panel. Joe and his children should only be tested if a gene is identified. D, Joe's brother should be tested using a long QT panel. If no mutation is found, Joe should be tested by whole exome sequencing. And E, a negative genetic test in Joe's brother means that both Joe's brother and Joe do not have long QT syndrome. So the correct answer here is C, Joe's brother should be tested using a long QT gene panel. Joe and his children should only be tested if a gene and a mutation are identified. So genetic testing for an unknown mutation in long QT syndrome has potential clinical benefit. It can direct clinical follow-up in the family. You can then identify affected people with a blood test. It can be done either using gene panels or whole exome sequencing. They give basically equivalent results. And for genotype positive individuals, if somebody, if a gene is identified, it can help direct medical therapy. So it can allow people to know who should avoid some medications that can cause acquired long QT syndrome. It can have some effects on exercise and treatment with beta blockers is highly effective for some types of long QT syndrome. Now, if an initial testing should always be done in somebody who is definitely clinically affected, if one does a genetic test in somebody who may or may not be affected, if the test is negative, and it is negative 50% of the time, then you don't know whether that person doesn't have an identifiable gene or whether they actually don't have long QT syndrome because they didn't inherit it. So you should always do the test in somebody who is definitively effective as possible. Now, if a causative mutation is identified, then it is appropriate to do cascade screening of first degree relatives, and then the first degree relatives of anybody who is affected. In addition, anybody in the family related who is clinically suspicious for by having symptoms or a funny electrocardiogram should be genetically tested. Now, if a causative mutation in an affected individual is not found, there's no reason to do further clinical genetic testing, you know, in anybody else in the family, because it basically means that the test cannot identify a causative gene. Now, whole exome sequencing can be used to look for new genes, but that's a research study and not used clinically in most patients for the time being. Now, Joe's brother clinically has long QT syndrome. Joe may or may not carry a long QT syndrome gene. Genetic testing should be done initially in Joe's brother. Case five, a 21-year-old man comes to you because he's concerned that he might be at risk for sudden death. His identical twin brother died suddenly one month ago. An autopsy was unremarkable. No tissue or blood samples are available from his brother. Neither he nor his brother had any medical history or any symptoms. However, a sister died at four months of age from sudden infant death syndrome. All of the following tests are appropriate except A, an electrocardiogram, B, a transthoracic echocardiogram, C, an electrophysiology study with programmed electrical stimulation, D, an exercise stress test without imaging, and E, genetic testing that is targeted based on the results of the clinical exam and the non-invasive testing. The best answer here is C, an electrophysiology study with programmed electrical stimulation would be the least indicated test. So if somebody presents with a history of sudden death or expectation that they might carry a gene associated with sudden death, which is obviously true for the identical twin of somebody who died suddenly, appropriate diagnostic tests would include a history, looking for a history of syncope, palpitations, aborted sudden death. A family history, looking for family history of not just of sudden death, but also of devices such as pacemakers and defibrillators and a history of heart failure. Now an electrocardiogram is useful and it's likely to show long QT syndrome, short QT syndrome, Brugada syndrome, arrhythmogenic right ventricular cardiomyopathy. Either echocardiography or cardiac MRI can show structural inherited syndromes including hypertrophic cardiomyopathy, dilated cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy. A stress test is useful to pick up long QT syndrome, especially long QT type 1, and catecholaminergic polymorphic ventricular tachycardia, which presents with a normal EKG, but arrhythmia is in the setting of exercise or stress. Drug testing is useful for Brugada syndrome using sodium channel blockers such as procainamide and for catecholaminergic polymorphic ventricular tachycardia using beta agonists. However, a program stimulation during an electrophysiology test may or may not have any diagnostic utility. It is used in Brugada syndrome to look for inducible ventricular fibrillation, but that is not diagnostic and is the least useful of the tests that were listed here. This is just a study that was published about 13 years ago now that looked at the diagnostic results following in people who presented with sudden death or aborted sudden death. And you can see that a little over half of people were able to get a diagnosis, and you can see that a lot of that diagnosis were these inherited cardiac syndromes, including long QT syndrome, Brugada syndrome, CPVT, hypertrophic cardiomyopathy, arrhythmogenic cardiomyopathy, and some non-inherited conditions. Case 6. A 30-year-old woman presents for evaluation due to a family history of sudden death. Her first cousin and her aunt on her mother's side in Holland died at young ages. Her aunt had heart failure and palpitations at the time of her death. Her mother died of cancer at age 42. Her EKG is shown below. Which of the following would not be an appropriate recommendation? A, cardiac MRI. B, hold the monitor. C, exercise restriction. D, ACE inhibitors if her left ventricular ejection fraction is significantly reduced. E, genetic testing independent of her cardiac MRI results. So the best answer here is E, genetic testing independent of her cardiac MRI results. So the woman most likely has arrhythmogenic right ventricular cardiomyopathy based on the history of arrhythmias and heart failure and the abnormal EKG, which has T inversions V1 to V3, which is one of the major criteria for ARVC. A cardiac MRI would pick up structural and functional right ventricular abnormalities that are associated with the condition, and a holder would likely identify premature beats and or not sustained ventricular tachycardia with a left bundle branch morphology, which would originate in the right ventricle. The importance of exercise restriction in most inherited conditions is uncertain. However, the one condition where exercise restriction has clearly been shown to help prevent the worsening of the condition is in fact arrhythmogenic right ventricular cardiomyopathy. So exercise high intensity exercise should be avoided in this condition. Left ventricular involvement is not uncommon in ARVC, especially when it's advanced, and it is now named arrhythmogenic cardiomyopathy with right ventricle, left ventricle, or both involvement. And this should be treated with goal-directed medical therapies as any other patient with a non-ischemic cardiomyopathy. Genetic testing should only be performed if the patient is definitively affected. And that would be based on the ARVC diagnostic criteria. And the diagnostic criteria, which have been updated in the last decade or so, include a major and minor criteria. And these criteria are based on IV wall motion, abnormalities and dilation, fibrous replacement of right ventricular myocytes on histology or autopsy, repolarization abnormalities on the EKG, depolarization abnormalities on the EKG, an epsilon wave, and an abnormal signal average DKG. Arrhythmias, usually of right ventricular origin with a left bundle branch block, and a family history of ARVC and or genetic evidence that a patient has ARVC. Case seven. You are seeing Frank, a 45 year old man with no medical history and no family history of arrhythmias or sudden death. His youngest daughter of three children had whole exome testing for multiple congenital abnormalities. And an incidental long QT syndrome mutation was found in the sodium channel SCN5A or NAV1.5. Frank was tested and carries the mutation. His EKG is shown below. Which of the following would you advise Frank? A, his EKG may be an example of incomplete penetrance. B, his EKG shows long QT syndrome. C, his EKG is abnormal, but no further evaluation is necessary. D, the mutation identified in Frank and his daughter probably does not cause long QT syndrome. And E, no further genetic screening of his family is necessary. So the best answer is A, his EKG may be an example of incomplete penetrance. So there are 56 genes which, if identified during whole genome or whole exome sequencing, are mandatory reporter genes, meaning that if a mutation is identified in one of those genes, they must be told to the patient and or the patient's family in the case of children. And many of the long QT and other inherited genes are on this list, including the cardiac sodium channel NAF1-5 and long QT syndrome mutations. For most inherited diseases, some individuals carry a pathologic mutation without showing the phenotype. This is the case for Frank. He carries a sodium channel SCN5A mutation, but has a normal QTC interval, most likely due to other genetic environmental factors that compensate for the extra late sodium current caused by the mutation. So this is an example of incomplete penetrance where the number of people with the phenotype is less than the number of people with the genotype. Frank is at risk for clinical long QT syndrome, but he doesn't have it. His EKG did show, however, an old inferior wall MI, which is an incidental finding. Now for Frank, coronary disease is actually much more dangerous to him than the incomplete penetrance of long QT syndrome, and he should be risk stratified and treated for his presumed coronary disease, and also advised to avoid QT prolonging drugs. Frank's two other children, each of which have a 50-50 chance of having the mutation, should be screened genetically and then clinically if they're shown to carry the mutation. While it's possible that the mutation was misclassified as causal, it's more likely that this is a case of incomplete penetrance and the mutation are in fact causal. And this is a list of some of the genes which are mandatory reported genes for in the case of whole eczema, whole genome sequencing. Okay, case A. Stephan is a 64-year-old man with hypertension, high cholesterol, and coronary disease, status post neonatary and non-QA of MI two years ago. He has no history of arrhythmias and no family history of sudden death. He developed a liver abscess with sepsis from which he is recovering. At an outpatient clinic visit with his infectious disease physician, he had a witness cardiac arrest and was resuscitated. His EKG following resuscitation is shown below. His medications at the time of the arrest included Plavix, fluconazole, Lasix, levofloxacin, metronidazole, and his potassium was 2.9 at the time of the arrest. A defibrillator was placed. A month later, his EKG is shown in the second tracing. At that time, his medications included aspirin, Plavix, Lasix, potassium, lisinopril, and topralexel. This is his EKG at the time of the arrest. And this is his EKG two months later. Which of the following best describes his situation? A, he has inherited Long QT syndrome and likely had Tursad causing the arrest. B, he has acquired Long QT syndrome and should undergo genetic testing using a commercial Long QT panel. C, he has acquired Long QT syndrome and requires no genetic testing. D, he is a healthy adult and should undergo genetic testing. D, he is at minimal risk of arrhythmias as long as potassium is greater than four. E, he has acquired Long QT syndrome from decreased depolarization reserve and is at risk for Brugada syndrome. So the best answer is C, he has acquired Long QT syndrome and requires no further genetic testing. So Stefan had marked prolonged QTc interval greater than 800 milliseconds at the time of his cardiac arrest. There were multiple potential contributing factors to this, including hypokalemia and three antibiotics, all of which have been associated with acquired Long QT syndrome, fluconazole, levofloxacin, and metronidazole. His EKG a month later off medications with a normal potassium had only borderline QTc prolongation at 450 milliseconds, making acquired Long QT syndrome the likely diagnosis here. Acquired Long QT syndrome is not commonly associated with mutations in the known Long QT genes and genetic testing in the absence of a family history or persistent QTc prolongation off drugs is not recommended. Acquired Long QT syndrome is caused by drugs binding to the pore of the HERG potassium channel, which is quite promiscuous for drug binding and is thought to represent diminished repolarization reserve. In other words, individuals susceptible to acquired Long QT syndrome have less outward potassium current than other individuals and blockade of HERG channel by the drugs brings out the condition. While hypokalemia likely contributed to the QTc prolongation and the arrest, it's not the only cause and Stefan should avoid QTc prolonging drugs in the future. Case nine. Frank is a 25 year old man who comes to you after his father had a cardiac arrest, was resuscitated and diagnosed with Brugada syndrome and had a defibrillator. Genetic testing identified a pathogenic mutation in SCN5A in Frank's father. Frank's EKG is shown below. Carrier testing showed that Frank does not carry the mutation identified in his dad. This is Frank's EKG. Possible explanations for Frank's negative genetic testing include all of the following except, A, Brugada syndrome is polygenic, B, Frank is not his father's biological son, incorrect paternity, C, incomplete penetrance and D, the variant identified in Frank's father is not actually a pathologic mutation that causes Brugada syndrome. The best answer here is C, this is not an example of incomplete penetrance. So carrier testing of Frank was appropriate because his father has Brugada syndrome and he is at risk for it and Frank actually has Brugada syndrome based on his EKG. So Frank's EKG shows spontaneous type one Brugada syndrome and you do not necessarily need symptoms to diagnose somebody with Brugada syndrome. So Frank has Brugada syndrome. Now Brugada syndrome is known to be polygenic. Thus, his father may have multiple genetic mutations and variants in addition to the SCN5A mutation so one or more of those other mutations or variants may have been transmitted to Frank and caused his Brugada syndrome even though he didn't get the SCN5A mutation. Now, Frank could have a different biological father that could be tested and the fact that both he and his identified parent both have Brugada syndrome could be a pure coincidence. Genetic testing and mutation identification is far from perfect. So it is possible that the SCN5A variant identified in Frank's father is actually not pathogenic and that he and his father share an unidentified Brugada syndrome mutation and genetic testing in Brugada syndrome only picks up less than 30% of causative mutations if you test somebody with Brugada syndrome. So, and while incomplete penetrance is common, it doesn't explain the presence of the disease phenotype in both Frank and his father because they're both affected. Case 10. So Timothy syndrome or Long QT type 8 is caused by mutations in the calcium channel gene CACNA1C, which encodes the channel CAV1.2. Which of the following statements best describes the pathogenesis of Timothy syndrome? CACNA1C mutations cause Long QT8 by decreasing outward calcium current. B, CACNA1C mutations cause Long QT8 by increasing inward calcium current. C, CACNA1C mutations cause Long QT8 by increasing the outward calcium activated potassium current and D, CACNA1C mutations cause Long QT8 by decreasing the inward calcium activated potassium current. The correct answer here is B, CACNA1C mutations cause Long QT syndrome by increasing the inward calcium current. So Timothy syndrome is a rare genetic disorder caused by prolonged, characterized by a prolonged QTC interval with malignant ventricular arrhythmias, autism, webbed fingers and toes syndactyly and abnormal facial features with small pointed teeth. A Timothy syndrome is caused by mutations in exon 8 or exon 8A of the calcium channel, the cardiac calcium channel CACNA1C that interfere with voltage dependent inactivation leading to increased inward current which prolongs the QT interval and also causes calcium overload. The CACNA1C channel is expressed in heart cells but also in neurons explaining the syndromic phenotype that affects both the heart and the brain and beta blockers, not calcium channel blockers are the treatment of choice for the cardiac effects of Timothy syndrome. The last case, case 11, you're asked to see a nine-year-old boy whose father died suddenly at age 32 and was diagnosed with Brugada syndrome. The father had a type one Brugada syndrome EKG pattern prior to his cardiac arrest and is heterozygous for a pathogenic mutation in the sodium channel gene SCN5A. His son also carries that mutation. Leads V1 to V3 of the son's baseline EKG are shown in the tracing below. The son now presents to the ER with a cough and a fever and the leads V1 to V3 of the repeat EKG in the ER are also shown. So on the left is his EKG at baseline at the time he was screened after his father was diagnosed and the EKG on the right shows his EKG in the ER at the time when he presented with a fever. Which of the following best describes the finding and management of this nine-year-old? A, neither EKG is diagnostic of Brugada syndrome. He can be sent home as he is at no significant risk for sudden death. B, he has Brugada syndrome and his EKG findings were exacerbated by the tachycardia. He should be admitted to the hospital and treated with beta blockers. C, he has Brugada syndrome and his EKG findings were exacerbated by the fever. He should be treated with Tylenol and admitted. Or D, he has Brugada syndrome and his EKG findings were exacerbated by the fever. He should be treated with quinidine and sent home if his EKG normalizes. So the best answer here is C. He has Brugada syndrome and his EKG findings were exacerbated by the fever. He should be treated with Tylenol and admitted. So the EKG pattern in Brugada syndrome is highly variable. It can be near normal one day and a type one fully affected pattern the next. It is exacerbated by fever. And this is one example of where fever has brought out a type one Brugada syndrome pattern in somebody who carries a known Brugada syndrome gene. The Brugada syndrome EKG pattern is exacerbated by beta blockers and beta blockers should not be used as a treatment to prevent arrhythmias. Fever can provoke both the EKG pattern and arrhythmias. Thus affected patients should be aggressively treated with antipyretics such as Tylenol and monitored if they develop a type one Brugada syndrome pattern, especially if they have symptoms such as syncope suggestive of arrhythmias. While quinidine by increasing outward potassium currents can normalize the EKG pattern in patients with Brugada syndromes and is useful in arrhythmic storm. There is no evidence supporting its use in primary prevention of arrhythmias and sudden cardiac death. Therefore it should not be used to prevent sudden death in cases of somebody who has Brugada syndrome at the present time. That is the last of the cases. Thank you very much. Hi there, welcome to workshop one. I'm Gordon Tomaselli at Albert Einstein College of Medicine. This workshop is going to focus on electrocardiographic and electrophysiologic correlations with some of the basic science information that you've heard in the basic science for clinicians lecture. So let's get right into it. These are my disclosures, and I'm on the scientific advisory board for the Leduc Foundation. None of those are relevant to this presentation. So let's start out with some questions. We're going to do questions rather than cases as these relate to basic science. So question number one, which of the following conditions is most likely responsible for the changes in the atrial action potential shown in gray here, as well as the rate dependence of the action potential duration shown in the plot below? Treatment A, the choices are A, treatment with dofetilide, B, left ventricular failure, C, interstitial fibrosis and electrical uncoupling of the myocytes, and D, rapid atrial pacing. We'll give you a few seconds to consider the answers. So the answer in this case is rapid atrial pacing. The reason being, treatment with dofetilide and the atrial changes associated with heart failure would tend to lengthen the atrial action potential duration. Here, the observation is shortening of the action potential duration over a range of pacing cycle lengths. Similarly, if you uncouple heart cells, both atria and ventricle, this tends to lead to an increase in action potential duration in the absence of input current from neighboring cells. Rapid atrial pacing, on the other hand, results in a reduction in both inward depolarizing currents, which would reduce action potential duration, as well as a reduction in depolarizing currents. The net effect is a reduction in action potential duration. So atrial electrical remodeling and atrial fibrillation is quite varied and really is a function of the underlying substrate. In rapid atrial pacing models, there's down-regulation of both repolarizing potassium currents, as well as depolarizing currents, such as calcium current. But on average, they're shortening of the action potential duration. In aging and structural heart disease, the atrial action potential duration may be modestly prolonged, but fibrosis is a prominent mechanistic feature, as is alterations in calcium homeostasis. So let's move on to question two. The changes in the action potentials shown in the figure below are most likely to be associated with which of the following? A, a pause-dependent onset. B, drugs with class III action. C, reactivation of L-type calcium channels. And D, calcium release from intracellular calcium stores. I'll give you a few seconds to consider the answers here as well. The answer is calcium release from intracellular calcium stores. The observation is a delayed after depolarization, that is a perturbation in membrane potential that occurs after completion of the action potential. These DADs, delayed after depolarizations, may be seen in situations with intracellular calcium overload and leaky ryanodine receptor channels. These are calcium release channels in the intracellular space. Rapid rates, catecholamines as might be elaborated in synthetic nervous system activation, and digitalis can produce DADs. They clinically are seen in digital toxicity and in some forms of structural heart disease. In contrast, early after depolarizations, which you heard about in the lecture, are associated with action potential prolongation, a pause-dependent onset, and are associated with torsade de plantes, polymorphic VT. Let's move on to the next question. The video shows the activation sequence of the left atrium during a tachycardia. Which of the following is most likely to be characteristic of this tachycardia? Decreasing conduction velocity will terminate the arrhythmia. Exaggerated dispersion of repolarization initiated the tachycardia. Increasing the wavelength to exceed the path length of the tachycardia will terminate the arrhythmia. An increase in late sodium current increases the likelihood of this arrhythmia. Again, let me give you a few seconds to consider the answer. So, increasing the wavelength to exceed the path length of the tachycardia will terminate the arrhythmia. Let's just go back to this for a second. This is a macro reentrant tachycardia around the scar in the left atrium. That's the observation. So this macro reentrant tachycardia around the scar in the posterior left atrium raises the concept of the relationship between the wavelength, which is the product of the conduction velocity and refractory period, to the path length, that is the anatomic site in which this tachycardia or activation wave has to fit. The path length, that is the anatomic length, has to exceed the functional length, the wavelength of the tachycardia to sustain reentrant. Now, decreasing conduction velocity will certainly reduce the wavelength of the tachycardia and may actually slow this SVT, but won't necessarily create the circumstances to terminate it. And modulation of conduction velocity as a therapeutic strategy certainly is something that can work, but usually what happens is you modulate conduction velocity enough to create a unidirectional block, bidirectional block in a reentrant circuit for termination. The dispersion of repolarization is often a predisposition to the generation of functional reentry, like in polymorphic VT, V for ventricular fibrillation, and H for fibrillation. Increasing the wavelength of the tachycardia to exceed the path length will not permit the arrhythmia to continue without the wave head colliding into the wave tail. This is the way this arrhythmia will be terminated. And an increase in late sodium current certainly increases the action potential duration and can be associated with an increase in functional reentry, but not excitable gap maximum reentry as in this case. Okay. Let's move on to the next question, question four. Cellular action potentials are recorded before in the dotted line and after in the solid line and intervention. Which of the following best explains the action potential duration or changes produced by the intervention? Devabradine or Corlander-induced IF blockade, adenosine activation of A1 receptors, late sodium channel block by rinolazine, or amiodarone-induced IKS blockade? I'll give you a few seconds to consider the answer here as well. Okay. The answer is adenosine activation of A1 receptors. So the observations here are an increase in the maximum diastolic potential, subtle shortening of the action potential duration, and a slowing of phase four diastolic depolarization. Avabradine, which is a funny channel or pacemaker current blocker will certainly slow phase four, but won't make the maximum diastolic potential more negative. Late sodium channel block by ranolazine is not likely to have a large impact and amiodarone certainly could slow phase four diastolic depolarization, but is likely to produce action potential prolongation. Adenosine by both direct and indirect effects will make the maximum diastolic potential more negative, slow phase four, and indeed shorten the action potential duration by its direct effects. That's illustrated in this cartoon. Adenosine is a nucleoside that's taken up by heart cells. It's metabolized both extracellularly and intracellularly by a number of enzyme systems. Adenosine itself can directly activate G-protein coupled receptors. These adenosine receptors are GI coupled, in fact. The G-protein coupled receptor has a direct effect on hyperpolarizing potassium currents, activating them in atrial and nodal tissue, resulting in shortening of the action potential duration. And the inhibitory G-protein also has an effect on adenylyl cyclase, inhibiting it, reducing the production of cyclic AMP and having anti-adrenergic effects, including inhibition of calcium current and shortening of the action potential duration. So multiple mechanisms of action of adenosine in the atrial and avian nodal tissue. By the way, adenosine is also taken up by heart cells in a diperiminal dependent fashion, and the effects of adenosine can be inhibited by methylzepines, like the alpha. Okay. Let's move on to the next question. Exposure to which of the following produced the changes in the ventricular action potentials in panel B compared to those in panel A? The potential answers are A, dronetarone, B, flecainide, C, esmolol, D, diltiazone. And let me give you a few seconds to consider the answer here as well. The answer is diltiazem. The observation here is that action potentials in A are long, and they're also interrupted by these early after depolarizations, interruptions in the normal smooth repolarization of the action potential itself. APD prolongation EADs are due to, or can be due to, reactivation of L-type calcium current. Both the action potential shortening, as well as the elimination of the early after depolarizations are the result of calcium channel block. Okay. Question six. 51-year-old woman presents with syncope without premonitory symptoms. She has a history of hypertension, substance abuse, and treated hepatitis C. Her medications include baby aspirin A, hydrochlorothiazide daily, nifedipine XL, 60 milligrams daily, and methadone, 100 milligrams daily. Her labs are remarkable for magnesium, 2.3 milligrams per liter, and a potassium 3.8 milliequivalents per liter. A trans thoracic echocardiogram revealed mild left ventricular hypertrophy with an ejection fraction of 65%. Her admission electrocardiogram is shown in this tracing. And a rhythm strip shortly after admission is shown in tracings 6.2 and 6.3. Let me show those to you. Which of the following is most likely responsible for the arrhythmia shown in tracing 6.2 and 6.3? Ischemia induced by cocaine use, decreased repolarizing reserve due to left ventricular hypertrophy, hypokalemia induced by hydrochlorothiazide, drug-induced QT prolongation, and a mutation in the HERD potassium channel. Let me give you a few seconds to consider the answers. And what I'll do is I'll actually scroll through to the baseline electrocardiogram and the monitor strip electrocardiogram. The answer is drug-induced prolonged QT. There are a number of things that could possibly have been associated with, sorry, with the arrhythmia shown in this tracing. And indeed, what you see is a long short initiation sequence of polymorphic ventricular tachycardia or torsad deployment. Ischemia induced by cocaine use certainly can produce torsad, but more likely will produce ventricular fibrillation. Decreased repolarizing reserve due to left ventricular hypertrophy certainly could be present, but in and of itself is not likely to produce torsad. The patient is not particularly hypokalemic, so hypokalemia induced by hydrochlorothiazide doesn't appear to be the answer here. And we have no evidence that she's got a mutation in the HERC channel, although certainly if she had one that was undetected, that could contribute to increased susceptibility. One of the things that really does occur and did occur in this case was that she had drug-induced QT prolongation, and the drug that produced QT prolongation was methadone. Methadone has a narrow toxic to therapeutic ratio and high concentrations of methadone. In fact, concentrations of methadone that are in the therapeutic window for preventing withdrawal also inhibit the HERC potassium channel and prolong the QT interval. There are a number of causes of QT interval prolongation, some of which are heritable, like mutations in 9-channel genes. You'll hear more about this in subsequent lectures. Severe grade accordion. There are central nervous system disorders, particularly intracranial bleeds that can produce QT interval prolongation, and medications and toxins, and there are many of them, but methadone is one that's particularly prominent. There are also myocardial diseases as well as metabolic abnormalities. When she was switched from methadone to another drug, buprenorphine, to prevent withdrawal, her electrocardiogram improved dramatically. It wasn't normal, but the QT interval dramatically decreased. Okay. Let's go to the next question. The figure shows the rate dependence of conduction velocity and action potential duration at 80% recovery, APD80, recorded in a monolayer of ventricular cardiomyocytes. Which of the following best explains the rate dependent effects on the conduction velocity and the APD80? Let me go to the recordings themselves. These are the recordings at three different pacing cycle lengths, increasing pacing cycle lengths from top to bottom. I'll come back to this in a second, but let me go back to the answers. A is sympathetic activation of repolarizing potassium currents. B, cumulative inactivation of delayed rectifier potassium currents. C, depletion of calcium from the sarcoplasmic reticulum with reduced calcium dependent inactivation of L-type calcium current. And D, cumulative inactivation of sodium current. Let me go back to the tracings and then I'll go back to the potential answers in just a second. So those are the observations. Back to the answers. Okay, so the answer is cumulative inactivation of sodium current. So the observation here is that with increasing pacing rate, there's slowed conduction velocity at the fastest rates in particular, and shortening of the action potential duration. So increasing rate, heart rate, will reduce the action potential duration. And in fact, for those of you that do pacing and program stimulation, will also reduce refractory periods in a number of ways. In intact animals and humans, synthetic activation is likely to be involved, but not so in this culture system, and is less likely to slow conduction. Cumulative activation, not inactivation, but activation of IKS will hasten repolarization and shorten phase three of the action potential duration, but inactivation will prolong the action potential duration and not much affect conduction velocity unless the action potentials are really excessively long. Increasing rate in a normal heart cell will increase and not deplete the SR of calcium, and enhanced calcium-dependent inactivation of L-type calcium currents may contribute to action potential duration shortening in this circumstances. Increasing rate can lead to cumulative inactivation of sodium current that would slow conduction. Think about rate-related bundle branch blocks, and inactivation of any component of the late sodium current would tend to shorten the APD. So this is the best answer of the group. Okay, let's move on to questioning. 23-year-old woman has a history of near syncope when running. Her sister died suddenly at age 16 at soccer practice. She has palpitations treated with Navalol, 40 milligrams daily, and a prior evaluation revealed an electrocardiogram shown in figure 8-1. She had a Holter monitor at this time as well, which revealed 230 PVCs in 24 hours, and on an exercise treadmill test, she exercised for 12 minutes to a peak heart rate of 190 beats per minute with PVCs at peak exercise and early recovery, similar to those shown in figure 8-2. Her sister had post-mortem genetic testing and revealed a type of ryanogen receptor mutation that was considered to be pathogenic or likely pathogenic in the poor foaming area, as well as a variant of uncertain significance in RYR2 as well. So she's now pregnant with twins entering her third trimester. She has more frequent palpitations at rest, but no syncope or near syncope, and monitoring reveals multiple morphology PVCs. Which of the following is most appropriate at this point? Increase her dose of Navalol and monitor, increase the dose of Navalol and provide a wearable defibrillator, add flecainide and monitor, add a calcium channel blocker and provide a wearable defibrillator, implant an implantable cardioverter defibrillator with minimal radiation. Let me give you a little time to consider the answers here as well. Okay. Increase the dose of Nadelol and provide a wearable defibrillator. Now, honestly, there may be a couple of ways to approach this problem. In fact, choice A might be reasonable, that is just to increase the dose of Nadelol and monitor, but the density of PVCs at rest is a concern and this risk is likely to increase in the postpartum period. Choice B is a conservative approach to get her through pregnancy, then consider more definitive therapy of risk dictates, including implanting of an implantable part of the defibrillator, although use of these devices and CPVT is not straightforward and other medications could be added more safely after pregnancy. There's limited use of flecainide in pregnancy with regard to safety and efficacy, but it could be added postpartum if needed. And in truth, this is in the third trimester, so not likely to be much in the way of triagenic effects, but to be safe, not using another drug in pregnancy like flecainide in pregnancy would be the safest course of action. Because of adverse hemodynamic effects on the fetus, calcium channel blockers should be avoided in pregnant women. And in the absence of symptoms at this point in her pregnancy, it's probably best to avoid an invasive procedure or even a subcutaneous ICD, although if needed, this could be done with acceptable risks to the fetus. So pregnancy and heritable arrhythmias, there's very little data. The data that's out there mostly deals with long QT syndrome. And it really highlights the notion that there's an increase in adverse effects, not only during pregnancy, but probably even more prominently in the postpartum period. The recommendation for long QT syndrome is to continue beta blocker therapy without interruption during pregnancy and after delivery. And this risk appears to be increased for nine months to a year afterwards. For CPVTS, in this case, there's very little data and similar medical treatment has been recommended. Okay. Question number nine. These CGs below were recorded during a stress test in a 43-year-old woman with type 1 myotonic dystrophy, with palpitations and worsening fatigue with exercise. She exercised for nine minutes on a treadmill and revealed, which revealed normal, I'm sorry, she exercised for nine minutes and a trans thoracic epipartygram during exercise revealed normal basal function and normal augmentation of all regions of the left ventricle. She's been treated with maxillotine, which significantly improved her symptoms of myotonia, dysphasia. Which of the following is the most appropriate next step? Now, these are the electrocardiograms reported during different stages of the treadmill exercise test, at rest, during stage two of exercise, and one minute post exercise. So which of the following is the most appropriate next step? Discontinued maxillotine, implantation of a permanent pacemaker, implantation of an implantable loop recorder, or continued routine follow-up? So the correct answer is implantation of a permanent pacemaker. The observation is that during exercise at rest, she had an electrocardiogram that was not normal. She had a left axis deviation, suggesting some conduction problems. And in fact, in this patient, this left axis deviation had been progressive. There are several approaches to this problem, but she did develop an intraventricular conduction delay with heart rates in excess of about 110 beats per minute. She was significantly improved on maxillotine and had been on maxillotine for a number of years and really didn't want to stop. So in order to safely continue this medication in the setting of a progressive development of conduction system disease, we elected to implant a permanent pacemaker. So myotonic dystrophy is often associated with cardiac arrhythmias. Sudden cardiac death has been reported in about 15% of patients with myotonic dystrophy. Some of it's bradycardic, but some of it's also ventricular tachycardia, ventricular fibrillation, as evidenced by the fact that some patients with pacemakers and myotonic dystrophy have experienced sudden cardiac death. Conduction block is frequent occurring in up to a quarter of patients with type one myotonic dystrophy. Again, so this is common and the course is very unpredictable. There is general, but not tight correlation with the degree of skeletal muscle involvement. Atrial fibrillation is also common and a minority of patients have left ventricular dilatation or systolic dysfunction. Very few, less than 5% will have heart failure symptoms. And a study published in the New England Journal of Medicine, Bill Rowe and colleagues, determined the frequency of severe electrocardiographic abnormalities in myotonic dystrophy, severe meaning excessively prolonged PR, QR restoration, or any other degree of AV block. And in six years of followup, severe ECG changes occurred in about 24% of people with myotonic dystrophy. And these were young folks, 54% were women, 20% of those folks had died and 7% had died of sudden cardiac death, again, in a relatively young cohort without much heart failure. So again, prominently involved in myotonic dystrophy is the conduction system of the heart. The treatment is supportive care for skeletal muscle disease, sodium channel blockers, and we've found maxillotin to be particularly useful for myotonia in patients with further skeletal muscle myotonia. Intraventricular conduction delays and AV block are relative contraindications and may mandate pacemaker implantation prior to using these drugs. Pacemaking should be considered and acquired complete AV block irrespective of symptoms, even if transient. Lower grade AV block because of the unpredictable progression. And there's also, due to conduction system delay in the ventricle, frequency of bundle branch reentrant tachycardia in myotonic dystrophy, particularly when the left ventricle has been involved. A couple of things about other management in this patient, anesthesia needs to be considered carefully and myotonia can be exaggerated by particular types of anesthetics, including depolarizing relaxants and antipolynesterases. And respiratory depression is a common finding in these patients. Let's consider the final question. The difference in the rate dependence of the action potential duration shown in the figure are best explained by which of the following. So these are action potentials from cells isolated from the anterior wall of the heart, control heart and failing heart, and the lateral wall of a control and failing heart. And these are the action potential cycle length plots that proliferation over a range of cycle lengths from cells in the anterior wall and from the lateral wall. Let me give you a few seconds to consider the answer. First, let me start with the answers. A is an increase in late sodium current in the lateral wall of both control and heart failure myocytes. B, a decrease in calcium current, most prominently in lateral heart failure cells. C, a reduction in rectified potassium current in heart failure cells from both the anterior and lateral walls. And D, reduced SR calcium loading in heart failure cells, most prominently in the lateral cells. So now let me have you consider the answers. Okay. Reduced SR calcium loading in heart failure cells, most prominently in lateral cells. So the observation is action potential prolongation in heart failure cells that's exaggerated in the lateral wall with a defect in rate dependent shortening of the action potential duration in the same cells. So an increase in late current would certainly produce action potential prolongation, but perhaps not the rate dependent effect. In addition, all cells in the lateral wall do not have a longer APD. A decrease in calcium current would shorten the action potential duration. Reduction in the end of rectified potassium current would tend to prolong, particularly the terminal portion of the APD, but not necessarily the rate dependence. Reduced SR calcium loading in heart failure would tend to decrease inactivation of calcium current, an effect that might be greatest at slowest rates. So this is, although some of these observations could be observed in heart failure, the best answer. So that concludes this workshop on electrocardiographic and electrophysiologic correlations in basic science. Thank you very much.
Video Summary
The video discussed various cases of cardiac conditions and their underlying mechanisms. One case involved acquired Long QT syndrome caused by medication use and hypokalemia. The presenter emphasized that genetic testing is not needed in the absence of a family history or persistent prolonged QT interval off drugs. The video also discussed Brugada syndrome, highlighting that genetic testing may not always identify the responsible mutation and that incomplete penetrance is common. Another condition discussed was Timothy syndrome, caused by mutations in the CACNA1C gene, which leads to prolonged QT interval and various symptoms. Overall, the workshop stressed the importance of understanding the mechanisms of cardiac conditions and their management through electrocardiographic and electrophysiologic correlations.
Keywords
cardiac conditions
underlying mechanisms
acquired Long QT syndrome
medication use
hypokalemia
genetic testing
prolonged QT interval
Brugada syndrome
responsible mutation
incomplete penetrance
Timothy syndrome
CACNA1C gene
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