Dilated Cardiomyopathy: Definition, Epidemiology, and Pathogenesis

00:01 Alright, that's the overview.

00:02 And if you've got that, then you've really understood about 80% of what we're going to be talking about.

00:07 The next 20% are going to be details that are important for you to take care of patients, and also to ace those board examinations.

00:16 Let's start with dilated cardiomyopathy.

00:19 We are looking at the the the schematic that we've used many, many times to show the various chambers of the heart.

00:26 We have the right sided heart all in blue.

00:29 The inferior and superior vena cava to the right atrium, to the tricuspid valve to the right ventricle, pulmonic valve going out to the lungs, and then returning, in pink, to the left atrium, through the pulmonary veins, across the mitral valve, into the left ventricle and out the aorta.

00:47 Okay.

00:49 In dilated cardiomyopathy, we get a progressive cardiac dilation for a variety of causes that we'll talk about.

00:58 It's associated not only with that dilation, but because we are stretching the cardiac myocytes, we are actually causing a rearrangement of the gap junctions that connect between the myocytes so there's electrical and mechanical dysfunction.

01:15 And overall, there's impaired systolic function, it just doesn't squeeze very well.

01:20 It is the most common cardiomyopathy causing about 90% of cases of cardiomyopathy not otherwise specified.

01:27 Most commonly diagnosed in 20's, to 50's, somewhere in that ballpark but in fact, you can have it much younger as we'll talk about.

01:35 You can have much later, as we'll talk about.

01:39 It is a lethal disease, one half of patients, 50% will be dead within a couple of years if not successfully treated, and only 25%, a quarter will survive longer than five years.

01:52 So this is as bad as or worse than many malignancies in terms of mortality.

02:01 Again, it's 50/50 roughly for the the causes of dilated cardiomyopathy, we'll cover first the non genetic causes.

02:09 So it turns out that infections, in particular, myocarditis will cause damage to the cardiac myocytes and then over a period of time, you may develop a dilated cardiomyopathy.

02:21 You may not even have recognized the original infection of the heart muscle.

02:27 But the consequences that we can see downstream, will nevertheless, chronically progress.

02:34 Toxic exposures, and this can be a variety of chemotherapy agents.

02:39 This can be heavy metals, this can be alcohol in alcohol use disorders.

02:45 So all of those can cause it.

02:48 A relatively, unfortunately rare cause non genetic cause of dilated cardiomyopathy is pregnancy.

02:54 So postpartum, or peripartum cardiomyopathy, and we'll talk a little bit about those mechanisms.

03:01 Ischemia.

03:01 So ischemic heart disease is probably one of the greater non-genetic causes and low levels of ischemia, not necessarily even frank infarction, but low levels of ischemia, can lead over time to progressive dysfunction with a dilated heart.

03:18 You can have something called Takotsubo cardiomyopathy.

03:21 This is the so-called "broken heart syndrome", due to stress.

03:27 And what do we mean by stress? We mean actually elevated catechols which cause microvascular spasm.

03:32 Microvascular spasm that lasts for greater than 20 to 30 minutes will cause microvascular infarct and then you get an ischemic cardiomyopathy.

03:41 So you can have stress cardiomyopathy, or Takotsubo.

03:45 Tachycardia.

03:46 So just having a very rapid heart rate for prolonged periods of time, can also cause dilated cardiomyopathy.

03:56 And the reason for that is it's part of high output failure.

04:02 It is actually a mechanism by which we can induce heart failure and experimental animals, just pace them very quickly.

04:08 And it is because over a period of time we've talked previously, the normal cardiac cycle, roughly a third of a second is going to be for systole, and two thirds of a second for diastole.

04:24 And if you have 60 beats per minute, that's kind of the the sequence, but now if I increase heart rates significantly - 120, 180 beats per minute, the systole stays the same, but the diastole shortens.

04:37 Remember, we only perfuse the heart during diastole.

04:40 So chronic tachycardia, chronic high output will actually drive a dilated cardiomyopathy due to ischemia.

04:48 Iron overload.

04:49 diseases like hemochromatosis, either whether it's primary or secondary, will also cause a dilated cardiomyopathy.

04:57 We'l ltalk about mechanisms shortly.

04:59 Let's look at the genetic causes.

05:02 Most of these are defects in a variety of proteins involved in the contractile apparatus of the sarcomeres.

05:10 And I will say, as we're getting more and more sophisticated, smarter and smarter and looking at more genes, we are finding increasing genetic causes of dilated cardiomyopathy, things that had previously been called idiopathic.

05:24 As they said, majority of these seem to be defects in force generation.

05:29 So the way that the actin and myosin fibers interact with each other or regulated by troponin and tropomyosin, we don't get affective sarcomeric contraction.

05:39 But some of the genetic causes involve signal defects that we're not getting the appropriate movement, say, of ions within the myocytes or it may even be defective ATP generation.

05:55 Regardless of the cause - genetic or non-genetic, in dilated cardiomyopathy, again, we overall have decreased myocardial contractility.

06:04 And the phenotype for all of these regardless includes dilation of the cardiac chambers, that's how we get the name dilated cardiomyopathy.

06:14 There is myocyte hypertrophy.

06:16 So in as we are getting less and less contractile, the response, the adaptation of the heart is to say, well, we we need to have stronger myocytes.

06:27 So even as we're getting less contractile force, the myocytes are undergoing hypertrophy, so they will be enlarged.

06:34 The abnormal volume and pressure will lead to the myofibroblast, the fibroblasts within the heart to lay down increased fibrosis that's going to also materially affect the contractility of the heart.

06:49 And because we have these dilated chambers with diminished movement of blood through them, they're going to be prone to developing thrombi which can eventually embolize