Inherited Arrhythmia

00:01 When we think about arrhythmias there can be acquired and heritable causes.

00:06 Of the acquired structural deficits, hypertrophic cardiomyopathy which may have a genetic basis but hypertrophy of the myocardium can be a cause of arrhythmias.

00:17 Mitral valve prolapse, which may be have heritable components as well, will be a cause, structural cause of arrhythmias.

00:26 And then arrhythmogenic cardiomyopathy, which also has an underlying congenital etiology, is something that occurs over time, and the patients will develop this.

00:37 It's acquired in terms of the structural defects.

00:40 There are heritable structural defects as well, congenital anomalies.

00:44 So ASD, VSD and other conduction bundle abnormalities in terms of the way that they're originally organized and put together can cause arrhythmias.

00:57 And then we're into the category of heritable chanelopathies.

01:02 And these are primary electrical disorders due to a variety of channel mutations.

01:09 Relatively rare cause, but a very important cause to recognize because if we know that a patient has one of these syndromes, then we can intervene with pacing devices and other ways to prevent them from having a sudden cardiac death.

01:24 The channelopathies, there are actually more than just the four listed here, but these are the four you should know about.

01:30 So there is a long QT syndrome where we have prolongation of the Q to T interval.

01:36 Inversely, we have a short QT syndrome associated with different channels, different functional mutations that give us a shorter QT interval.

01:45 We have Brugada syndrome, and then we have the catecholaminergic polymorphic ventricular tachycardia syndrome, much easier to say CPVT that will also cause, is a chanellopathy, it will cause arrhythmias.

02:01 Each of these have a slightly different presentation and clinical story, and we're going to cover those shortly in a moment.

02:10 The channelopathies are really interesting, they're predominately autosomal dominant disorders, so if you have a mutation in one gene from one parent, you have a 50 percent, you have the disease and you'll get it 50% of the time.

02:25 Most of the genes encode either ion channels, and it can be calcium channels, potassium channels, sodium channels or accessory proteins that are responsible for opening and closing and regulating the function of those channels.

02:39 The defective channels interfere with the normal signal transduction within the myocyte, so this is not normally, these are not normally channelopathies that affect the conduction system, but rather affect the individual cardiac myocytes at that level where we're getting cell to cell to cell propagation of a signal.

03:01 Here are the kind of disorders and the causes and the manifestations.

03:05 So long QT syndrome is associated with either potassium channel loss of function, so you're not moving potassium ions appropriately, or gain of function in the sodium channel.

03:18 And particularly the gain of function mutations in the sodium channel involve a particular sodium channel called the SCN5A sodium channel.

03:28 Short QT syndrome is associated with either gain or loss of function of potassium channel, and there are a number of potassium channels, so there are variations on this overall theme.

03:41 Brugada syndrome is associated with a loss of function of the sodium channel.

03:46 It's the same sodium channel where a gain of function gave us the long QT syndrome, or it can be due to loss of function of a calcium channel.

03:54 So there, I hope that you're getting the sensation or getting the impression that there can be a lot of mutations in multiple channels that can give similar manifestations of a syndrome.

04:05 So if we say someone has a Brugada syndrome, for example, they may have loss of function in the sodium channel, or they could have a loss of function in a calcium channel.

04:16 It gets a little bit confusing, just remember these four.

04:20 And then you have the catecholaminergic polymorphic ventricular tachycardia, CPVT syndrome, which is a different receptor.

04:29 This is the Ryanodine receptor that's going to be responsible for regulating calcium ion movement, and it's typically a gain of function mutation in that.

04:39 Okay, how do these patients present? So the long QT syndrome is progressive, excessive prolongation of a cardiac repolarization.

04:50 So we are taking longer and longer and longer to get everything repolarized.

04:55 The manifestations are a stress-induced syncope, so you actually have to have other signals, hormonal signals, for example, that induce this.

05:06 Arrhythmia, the long QT may exist at baseline, but the sudden cardiac death that can result from them is something that is tends to be stress induced.

05:16 Shirt QT syndrome, so we have an abbreviated repolarization interval.

05:20 Patients will describe palpitations, they may have syncope, they may have sudden cardiac death.

05:24 If we look at their normal EKG in the absence of anything else, we will see that the QT interval is shortened.

05:31 That's how we make the diagnosis.

05:33 But the actual manifestations, the palpitations, syncope and sudden cardiac death may only come out with certain stressors.

05:42 Brugada syndrome is presented or presents with ST segment elevation, so we're getting aberrant, repolarization.

05:51 We also tend to see right bundle branch block.

05:54 Patients may present with syncope or sudden cardiac death during rest or sleep.

05:59 And then finally, the CPVT syndrome, no characteristic findings, particularly in terms of the ECG, but if we have stress catecholaminergic stimulus with a lot of catechols circulating, that may cause a life threatening arrhythmia, particularly in childhood.