WEBVTT 00:00:07.069 --> 00:00:10.279 The topic of our conference this afternoon 00:00:10.279 --> 00:00:12.409 is is a very important one 00:00:12.409 --> 00:00:13.789 namely, heart 00:00:13.789 --> 00:00:15.959 failure 00:00:15.959 --> 00:00:19.096 and its important, as you'll hear from my colleagues, 00:00:19.096 --> 00:00:24.082 for a number of reasons. The sheer prevalence of heart failure in our population 00:00:24.082 --> 00:00:25.009 says that 00:00:25.009 --> 00:00:29.079 you're going to deal with a tremendous numbers of patients having 00:00:29.079 --> 00:00:30.449 related problems. 00:00:30.449 --> 00:00:31.769 The associated 00:00:31.769 --> 00:00:36.056 morbidity and mortality is very significant and 00:00:36.056 --> 00:00:40.095 heart failure, one way or another, consumes a very, very significant 00:00:40.095 --> 00:00:43.055 fraction of our health care resources. 00:00:43.055 --> 00:00:46.057 So it's a problem that you're going to be dealing with 00:00:46.057 --> 00:00:48.092 a lot of the time. 00:00:48.092 --> 00:00:51.068 I will spend my time 00:00:51.068 --> 00:00:55.008 just introducing the general concept which we've had a little 00:00:55.008 --> 00:00:58.044 bit in lecture, but will try to embellish that 00:00:58.044 --> 00:01:02.007 and illustrate some of the pathologic anatomy associated with heart 00:01:02.007 --> 00:01:03.082 failure one way or another. 00:01:03.082 --> 00:01:07.026 Then I'll pass the baton to Dr Matthews 00:01:07.026 --> 00:01:11.095 who will make clinical reality out of this 00:01:11.095 --> 00:01:16.004 and translate all of this into signs and symptom that the patients manifest 00:01:16.004 --> 00:01:16.091 and 00:01:16.091 --> 00:01:19.086 appropriate strategies 00:01:19.086 --> 00:01:23.034 of medical therapy and then we will conclude the afternoon with 00:01:23.034 --> 00:01:25.033 Dr Jonathan Haft 00:01:25.033 --> 00:01:28.077 and with the participation of a patient of his 00:01:28.077 --> 00:01:32.008 and discuss the treatment of advanced heart failure 00:01:32.008 --> 00:01:36.036 with mechanical support and cardiac transplantation. 00:01:36.036 --> 00:01:37.044 So that's 00:01:37.044 --> 00:01:42.051 the agenda for this afternoon. 00:01:42.051 --> 00:01:43.034 Now in its 00:01:43.034 --> 00:01:47.098 very simple definition, and there are a lot of ways to define it, the very simple 00:01:47.098 --> 00:01:50.018 definition of heart failure 00:01:50.018 --> 00:01:53.002 involves the inability of the heart 00:01:53.002 --> 00:01:55.729 to meet 00:01:55.729 --> 00:02:00.033 to really pump sufficient blood to meet the metabolic needs of 00:02:00.033 --> 00:02:02.012 the body. 00:02:02.012 --> 00:02:06.056 Now this can happen in a in a variety of ways. 00:02:06.056 --> 00:02:10.589 It can come to pass, and this isn't as frequent, that the 00:02:10.589 --> 00:02:14.579 heart is putting out a normal or even an excessive amount of blood. 00:02:14.579 --> 00:02:16.659 It's really pumping it out there, but it's being 00:02:16.659 --> 00:02:18.051 driven by 00:02:18.051 --> 00:02:23.009 an increased demand in the peripheral tissues that it just can't keep up with. 00:02:23.009 --> 00:02:26.439 This sort of thing we see in thyrotoxicosis. 00:02:26.439 --> 00:02:28.059 It used to be seen, 00:02:28.059 --> 00:02:31.789 we don't see it much any more thankfully, in beriberi - vitamin deficiency 00:02:31.789 --> 00:02:33.659 with vasodilatation 00:02:33.659 --> 00:02:36.409 all over the place and the heart just couldn't keep up with 00:02:36.409 --> 00:02:37.042 that volume 00:02:37.042 --> 00:02:38.139 of the 00:02:38.139 --> 00:02:40.209 cardiovascular system. 00:02:40.209 --> 00:02:45.839 It's seen occasionally with arteriovenous fistulas 00:02:45.839 --> 00:02:49.559 that dump a lot of blood directly from arteries into the veins in the heart 00:02:49.559 --> 00:02:52.709 The heart just can't keep up. Or severe anemia. 00:02:52.709 --> 00:02:56.499 Those sorts of things will result in what we call a high output sort of failure, 00:02:56.499 --> 00:02:57.489 but much more 00:02:57.489 --> 00:02:59.119 often, we're dealing with 00:02:59.119 --> 00:03:00.085 the problem of 00:03:00.085 --> 00:03:03.799 not enough blood being ejected 00:03:03.799 --> 00:03:06.269 for one reason or another 00:03:06.269 --> 00:03:11.359 from the heart to support even normal demands 00:03:11.359 --> 00:03:15.039 and this is a combination really of 00:03:15.039 --> 00:03:18.489 the loss of systolic umph, 00:03:18.489 --> 00:03:22.069 in other words, the contracting heart just can't get it out there 00:03:22.069 --> 00:03:23.059 in the way it should and 00:03:23.059 --> 00:03:27.052 often this can be accompanied by 00:03:27.052 --> 00:03:29.069 diastolic, 00:03:29.069 --> 00:03:34.279 i've listed it here as diastolic failure but it's a difficulty in diastolic filling 00:03:34.279 --> 00:03:38.419 which can impair the heart action. If the heart muscle can't relax and is ineffective 00:03:38.419 --> 00:03:39.004 it's stiff 00:03:39.004 --> 00:03:40.459 it won't 00:03:40.459 --> 00:03:41.809 accept 00:03:41.809 --> 00:03:44.009 the right volume coming into it and that's going to lead 00:03:44.009 --> 00:03:46.989 also to failure. 00:03:46.989 --> 00:03:52.229 One way or another, these factors can lead to a constellation 00:03:52.229 --> 00:03:54.033 of signs and symptoms, 00:03:54.033 --> 00:03:57.009 we'll get to that at the end. 00:03:57.009 --> 00:04:00.689 It's really related on the one hand to congestion of organs which you know all 00:04:00.689 --> 00:04:02.439 about now after 00:04:02.439 --> 00:04:02.095 your 00:04:02.095 --> 00:04:08.034 lectures in pathology and hypoprofusion of tissues which 00:04:08.034 --> 00:04:10.099 we haven't emphasized as much, but it's a 00:04:10.099 --> 00:04:13.068 very important point. 00:04:13.068 --> 00:04:18.659 Now, when we look at the causes of heart failure and there are many, many of them, far more 00:04:18.659 --> 00:04:20.869 than we can talk about, 00:04:20.869 --> 00:04:22.319 but 00:04:22.319 --> 00:04:25.819 if we look at those situations where there is 00:04:25.819 --> 00:04:28.061 some unusual demand 00:04:28.061 --> 00:04:31.041 on the heart, and the heart just can't meet it, they 00:04:31.041 --> 00:04:33.229 fall into a number 00:04:33.229 --> 00:04:35.319 of categories, and I will 00:04:35.319 --> 00:04:37.919 illustrate each of these in a moment, 00:04:37.919 --> 00:04:41.028 but one very important category is resistance 00:04:41.028 --> 00:04:42.759 to flow, in other words, 00:04:42.759 --> 00:04:46.769 if something is keeping the flow of blood from going so 00:04:46.769 --> 00:04:50.879 the heart has to work harder to push it past that resistance 00:04:50.879 --> 00:04:55.629 it will come to the point where the heart could no longer do it and it fails. 00:04:55.629 --> 00:04:59.009 Another problem is what we call regurgitant flow, I mean you like to think of the 00:04:59.009 --> 00:05:03.979 blood flowing in one direction through the cardiovascular system, but 00:05:03.979 --> 00:05:05.769 sometimes it comes to pass where, at a point, 00:05:05.769 --> 00:05:06.007 there's 00:05:06.007 --> 00:05:09.089 regurgitation, instead of things pulsing forward, they slosh 00:05:09.089 --> 00:05:11.569 backward, and that 00:05:11.569 --> 00:05:16.439 imposes a strain on the heart as you will see 00:05:16.439 --> 00:05:21.037 and thirdly and very importantly there is disease of various sorts, lots of sorts, 00:05:21.037 --> 00:05:25.439 targeting the myocardium itself 00:05:25.439 --> 00:05:29.015 so that there's no resistance to flow, there's no regurgitant flow 00:05:29.015 --> 00:05:29.999 perhaps, but the 00:05:29.999 --> 00:05:32.559 heart muscle is sick. 00:05:32.559 --> 00:05:34.019 And finally, we won't talk 00:05:34.019 --> 00:05:38.079 at all about this, I won't, about conduction abnormalities 00:05:38.079 --> 00:05:40.064 which can also lead to decompensation 00:05:40.064 --> 00:05:42.018 of the heart. 00:05:42.018 --> 00:05:43.369 Now, I'd like 00:05:43.369 --> 00:05:46.619 to illustrate some of these very quickly, don't get lost in the details, 00:05:46.619 --> 00:05:47.069 just 00:05:47.069 --> 00:05:51.047 let it flow over you, you're going to get these details later on 00:05:51.047 --> 00:05:52.097 in the year 00:05:52.097 --> 00:05:57.509 later on in your careers, but just for a little orientation, 00:05:57.509 --> 00:06:03.011 I'll give you an example first of resistance to flow, 00:06:03.011 --> 00:06:04.709 there is a good hallmark for 00:06:04.709 --> 00:06:08.309 it, I can't show you hypertension obviously 00:06:08.309 --> 00:06:09.179 but think of 00:06:09.179 --> 00:06:14.559 the situation when a patient has established significant hypertension, 00:06:14.559 --> 00:06:16.081 it means that 24/7 00:06:16.081 --> 00:06:19.759 every minute, every beat of the heart 00:06:19.759 --> 00:06:24.219 that poor left ventricle is having to force against an increased resistance to flow, 00:06:24.219 --> 00:06:25.003 that's what hypertension 00:06:25.003 --> 00:06:27.509 is all about. The result 00:06:27.509 --> 00:06:28.008 00:06:28.008 --> 00:06:32.028 one of the results you see here is is this rather massive 00:06:32.028 --> 00:06:34.048 myocardial hypertrophy which i'm sure you all recognize, 00:06:34.048 --> 00:06:35.969 so that's one 00:06:35.969 --> 00:06:40.036 kind of resistance to flow. Here's another one, this takes a 00:06:40.036 --> 00:06:44.919 little explaining, it's an unusual plane of section of the heart, 00:06:44.919 --> 00:06:48.289 but what attracts your attention right away is that the left ventricle 00:06:48.289 --> 00:06:51.009 is immensely hypertrophied, very thick 00:06:51.009 --> 00:06:52.819 and very heavy, and the reason 00:06:52.819 --> 00:06:56.479 for it is not terribly well shown here 00:06:56.479 --> 00:07:00.849 but here is the aortic outflow, this is the aorta here, and this would be the aortic valve 00:07:00.849 --> 00:07:03.005 which you can't get a good view of, but 00:07:03.005 --> 00:07:08.043 a common lesion is stenosis of the aortic valve, 00:07:08.043 --> 00:07:13.024 and obviously, in that situation, it's very analogous to hypertension, every time 00:07:13.024 --> 00:07:16.159 the ventricle contracts, it's got to push that blood 00:07:16.159 --> 00:07:18.449 through a stenotic valve 00:07:18.449 --> 00:07:20.269 and it's a lot of work. 00:07:20.269 --> 00:07:23.839 I'll show you one of these valves from above, this is an interesting one, 00:07:23.839 --> 00:07:27.849 this is a pretty typical example of aortic stenosis, 00:07:27.849 --> 00:07:31.004 you're standing in the ascending aorta, looking back 00:07:31.004 --> 00:07:33.859 towards the left ventricle, and 00:07:33.859 --> 00:07:39.939 you're aware from your gross anatomy that this should be a three cusp valve 00:07:39.939 --> 00:07:42.033 and you're seeing a couple of things here, 00:07:42.033 --> 00:07:45.129 first of all this is only two cusps 00:07:45.129 --> 00:07:47.009 and that was a congenital problem 00:07:47.009 --> 00:07:50.279 and it's a fairly frequent one in our population, there are probably a 00:07:50.279 --> 00:07:51.499 couple of so-called 00:07:51.499 --> 00:07:53.699 bicuspid valves in this room 00:07:53.699 --> 00:07:55.499 and 00:07:55.499 --> 00:07:57.009 whatever the case 00:07:57.009 --> 00:08:01.021 the aortic valve is very susceptible to calcification 00:08:01.021 --> 00:08:04.119 and stiffening with age, and if you 00:08:04.119 --> 00:08:07.969 plot it against the aging population, we see an increasing 00:08:07.969 --> 00:08:09.409 incidence of stenotic 00:08:09.409 --> 00:08:11.319 aortic valves even if they're not 00:08:11.319 --> 00:08:15.409 bicuspid, if they're congenitally bicuspid like this they get wrecked 00:08:15.409 --> 00:08:16.689 very frequently 00:08:16.689 --> 00:08:18.609 earlier on so that 00:08:18.609 --> 00:08:21.959 instead of maybe in the seventies or eighties, it might be in the 00:08:21.959 --> 00:08:24.049 fifties and sixties that the patient would suffer from such stenosis. 00:08:24.049 --> 00:08:25.006 But you can see 00:08:25.006 --> 00:08:26.919 that every time 00:08:26.919 --> 00:08:30.004 the ventricle is trying to push blood through that orifice, and it's really like brick 00:08:30.004 --> 00:08:31.619 it doesn't move. 00:08:31.619 --> 00:08:32.082 It's going to be a 00:08:32.082 --> 00:08:37.024 tremendous load on the left ventricle. 00:08:37.024 --> 00:08:41.047 here's another valve stenosis for you, we don't see this as much anymore, 00:08:41.047 --> 00:08:45.093 it's a result usually of old rheumatic fever in childhood, but the mitral valve 00:08:45.093 --> 00:08:50.001 here is reduced to a fish mouth, it's all puckered up 00:08:50.001 --> 00:08:54.035 and scarred, and frequently calcified, 00:08:54.035 --> 00:08:55.649 and the valve leaflets 00:08:55.649 --> 00:08:57.026 can't move at all, 00:08:57.026 --> 00:08:59.096 so that the blood coming out of the lungs into the 00:08:59.096 --> 00:09:01.059 into the left atrium trying to get through 00:09:01.059 --> 00:09:04.039 into the left ventricle, you're looking down towards the left ventricle, 00:09:04.039 --> 00:09:08.072 it's got to pass by that stenotic slit. 00:09:08.072 --> 00:09:10.009 The result is damming back, 00:09:10.009 --> 00:09:15.043 very obviously you know about passive congestion, you can see this immensely dilated 00:09:15.043 --> 00:09:16.017 left atrium 00:09:16.017 --> 00:09:17.003 and you can imagine 00:09:17.003 --> 00:09:20.007 what was happening in the lungs 00:09:20.007 --> 00:09:21.669 behind that sort of obstruction. 00:09:21.669 --> 00:09:22.082 Now as far as 00:09:22.082 --> 00:09:25.094 regurgitant flow, hold on with me 00:09:25.094 --> 00:09:30.035 and i'll try to explain it, here is another mitral valve, we've chopped off the 00:09:30.035 --> 00:09:32.004 the atrium and you're looking right at the 00:09:32.004 --> 00:09:34.088 mitral valve, and 00:09:34.088 --> 00:09:38.023 think about what you saw in gross anatomy, the mitral valve leaflets usually come together 00:09:38.023 --> 00:09:41.003 like that and keep the blood, during systole, 00:09:41.003 --> 00:09:45.023 keep the blood from flowing back into the atrium so all the blood goes out 00:09:45.023 --> 00:09:47.044 the aorta like it should. 00:09:47.044 --> 00:09:49.071 Here, 00:09:49.071 --> 00:09:54.084 and this happens for a variety of reasons, but here this leaflet of the valve 00:09:54.084 --> 00:09:57.043 is sort of pooched up and 00:09:57.043 --> 00:10:02.071 and with every ventricular systole, blood is able to force its way back 00:10:02.071 --> 00:10:04.048 into the atrium, which means 00:10:04.048 --> 00:10:08.015 the poor old left ventricle is pumping some of that blood more than once 00:10:08.015 --> 00:10:11.063 in other words it's putting part of it out the aorta, part of it back up the atrium, 00:10:11.063 --> 00:10:12.044 and that comes 00:10:12.044 --> 00:10:14.047 sloshing down for the next 00:10:14.047 --> 00:10:16.028 beat of the heart 00:10:16.028 --> 00:10:18.084 and it consists, 00:10:18.084 --> 00:10:22.649 it induces a volume overload on the valve 00:10:22.649 --> 00:10:24.075 and 00:10:24.075 --> 00:10:26.059 on the ventricle 00:10:26.059 --> 00:10:29.016 and it may fail. 00:10:29.016 --> 00:10:33.026 Now when you get to the realm of myocardial abnormality per se, in other words disease of the myocardium 00:10:33.026 --> 00:10:34.098 00:10:34.098 --> 00:10:36.022 there are lots 00:10:36.022 --> 00:10:42.012 and lots of examples, and the most frequent one and most important one is myocardial ischemic disease 00:10:42.012 --> 00:10:46.098 in other words, the result of coronary artery disease, atherosclerosis 00:10:46.098 --> 00:10:50.062 and its complications, and what happens when the myocardium 00:10:50.062 --> 00:10:52.001 becomes ischemic. 00:10:52.001 --> 00:10:55.075 Clearly many patients who have a myocardial infarct, an acute heart attack 00:10:55.075 --> 00:10:56.095 will go into 00:10:56.095 --> 00:11:01.012 acute failure if enough of the myocardium is involved right then and there in the 00:11:01.012 --> 00:11:04.023 emergency room. 00:11:04.023 --> 00:11:06.097 But chronically it can become a big problem even when the 00:11:06.097 --> 00:11:11.057 situation heals. Here, for example, 00:11:11.057 --> 00:11:15.045 a slice of a heart, this is left ventricle over here, 00:11:15.045 --> 00:11:19.012 and this individual sustained a myocardial infarct, I don't know how long ago, 00:11:19.012 --> 00:11:20.089 it could be years ago, 00:11:20.089 --> 00:11:25.014 months ago, and you see a lot of scar 00:11:25.014 --> 00:11:28.022 throughout the ventricular wall, a little bit back there, a little bit in the septum, 00:11:28.022 --> 00:11:31.005 but a tremendous scar here 00:11:31.005 --> 00:11:36.399 and when this involves enough of the ventricular myocardium, it puts a strain 00:11:36.399 --> 00:11:39.056 on what's left of viable myocardium, because this 00:11:39.056 --> 00:11:43.000 obviously doesn't contract. 00:11:43.000 --> 00:11:47.005 Patients can sustain a lot of myocardial infarcts, 00:11:47.005 --> 00:11:52.025 here's serial sections of the same heart, and you can see at least a couple of infarcts 00:11:52.025 --> 00:11:52.809 that involve 00:11:52.809 --> 00:11:54.015 a tremendous 00:11:54.015 --> 00:11:55.072 fraction of the 00:11:55.072 --> 00:11:56.024 left ventricle 00:11:56.024 --> 00:11:57.093 and again when 00:11:57.093 --> 00:11:59.639 that happens, the rest of 00:11:59.639 --> 00:12:02.048 this can't keep up with it, and the left 00:12:02.048 --> 00:12:04.083 ventricle fails. 00:12:04.083 --> 00:12:06.059 Here is a heart that was 00:12:06.059 --> 00:12:09.093 was removed from a patient who was still alive 00:12:09.093 --> 00:12:12.071 happy and well as far as i know 00:12:12.071 --> 00:12:15.073 This is an explant to the heart, in other words, taken out of the time of transplantation 00:12:15.073 --> 00:12:16.889 and this was also 00:12:16.889 --> 00:12:19.239 ischemic disease, and this 00:12:19.239 --> 00:12:22.459 individual had scraped through 00:12:22.459 --> 00:12:26.083 with this much of the heart converted into 00:12:26.083 --> 00:12:29.085 what amounted to a fibrous sack, totally 00:12:29.085 --> 00:12:32.021 non-contractile 00:12:32.021 --> 00:12:36.006 and you can see there's even a clot in there because it wasn't moving 00:12:36.006 --> 00:12:37.002 and that had 00:12:37.002 --> 00:12:41.018 produced failure of the remaining myocardium. 00:12:41.018 --> 00:12:42.093 So that's a 00:12:42.093 --> 00:12:45.002 good sample of 00:12:45.002 --> 00:12:46.012 ischemic 00:12:46.012 --> 00:12:49.021 disease leading to chronic failure of the left ventricle. 00:12:49.021 --> 00:12:49.679 00:12:49.679 --> 00:12:51.084 Now, beyond 00:12:51.084 --> 00:12:55.017 ischemic disease there are a whole lot of them, don't worry about the details 00:12:55.017 --> 00:12:58.092 I'll show you this as an example of an inflammatory process targeted at 00:12:58.092 --> 00:13:01.013 the myocardium. We see this 00:13:01.013 --> 00:13:05.049 with certain viral infections, certain protozoan infections, 00:13:05.049 --> 00:13:06.074 with bacterial 00:13:06.074 --> 00:13:11.004 infections, but you can get inflammation of the myocardium 00:13:11.004 --> 00:13:13.076 and you can almost literally hear 00:13:13.076 --> 00:13:16.018 these cells chewing at the myocytes 00:13:16.018 --> 00:13:18.025 and obviously 00:13:18.025 --> 00:13:22.059 obviously that can produce failure. 00:13:22.059 --> 00:13:25.049 We see that not infrequently, 00:13:25.049 --> 00:13:29.048 then the heart can be involved in a variety of systemic diseases, in other words 00:13:29.048 --> 00:13:32.097 you can have something going on affecting many tissues in 00:13:32.097 --> 00:13:36.041 the body, but that something may affect the heart and produce 00:13:36.041 --> 00:13:37.669 failure. Here's an example 00:13:37.669 --> 00:13:39.093 now I don't know 00:13:39.093 --> 00:13:44.021 if I want to dart in the auditorium completely to show you this 00:13:44.021 --> 00:13:49.093 did you discuss hemochromatosis in genetics? Yes? Not a complete blank. 00:13:49.093 --> 00:13:52.025 00:13:52.025 --> 00:13:56.016 It's an ineffective storage disease because the body absorbs too much iron 00:13:56.016 --> 00:13:56.083 from the gut, 00:13:56.083 --> 00:13:58.003 and the iron 00:13:58.003 --> 00:14:01.087 gets stored in a variety of issues and one of the tissues it gets stored in 00:14:01.087 --> 00:14:03.066 is the heart, 00:14:03.066 --> 00:14:07.024 and you recognize instantly that this is myocardium 00:14:07.024 --> 00:14:11.021 and as you stare at it a little bit, you'll pick out some nice golden brown pigment 00:14:11.021 --> 00:14:16.045 there and there and there, you see a little more over there, and little bit down there and over there. 00:14:16.045 --> 00:14:18.071 and one of the pigments 00:14:18.071 --> 00:14:21.088 you'd think of in the heart, someone asked me a question about this last week, 00:14:21.088 --> 00:14:25.052 it would be lipofuscin (wear and tear pigment) 00:14:25.052 --> 00:14:30.066 but another pigment you got to think about is iron, and this is stored iron 00:14:30.066 --> 00:14:31.989 in this myocardium. Here is 00:14:31.989 --> 00:14:33.038 that blue 00:14:33.038 --> 00:14:37.099 Prussian blue iron stain, tremendous iron 00:14:37.099 --> 00:14:38.096 load, iron is bad for you 00:14:38.096 --> 00:14:44.024 if it gets deposited in certain tissues. This can produce myocardial failure. 00:14:44.024 --> 00:14:46.089 This was from a relatively young man who presented with 00:14:46.089 --> 00:14:49.004 very advanced heart failure 00:14:49.004 --> 00:14:51.013 because of his unrecognized 00:14:51.013 --> 00:14:52.004 hemochromatosis. 00:14:52.004 --> 00:14:54.056 00:14:54.056 --> 00:14:55.009 One other that you will hear about 00:14:55.009 --> 00:14:58.045 probably next year 00:14:58.045 --> 00:15:01.026 is amyloidosis. Amyloid 00:15:01.026 --> 00:15:02.109 00:15:02.109 --> 00:15:06.058 is an abnormal protein that could get deposited in a number of tissues 00:15:06.058 --> 00:15:08.082 for a number of reasons, which I won't go into. 00:15:08.082 --> 00:15:10.149 But all of this 00:15:10.149 --> 00:15:15.002 sort of translucent, gray stuff surrounding the 00:15:15.002 --> 00:15:19.066 myocytes, you're looking at a cross-sectional view of myocardium, 00:15:19.066 --> 00:15:23.049 and you can see that each myocyte is enveloped in this 00:15:23.049 --> 00:15:24.062 casing 00:15:24.062 --> 00:15:26.035 of amyloid. 00:15:26.035 --> 00:15:27.063 And this is 00:15:27.063 --> 00:15:31.007 a marvelous example of something that renders the heart rigid 00:15:31.007 --> 00:15:31.093 and unable to 00:15:31.093 --> 00:15:34.074 expand diastolically, and it can be 00:15:34.074 --> 00:15:36.063 a cause of heart failure. 00:15:36.063 --> 00:15:38.092 Finally, 00:15:38.092 --> 00:15:41.061 this is not a complete list, I'm just showing 00:15:41.061 --> 00:15:43.006 the examples, there are 00:15:43.006 --> 00:15:47.082 a number of genetic diseases of the heart muscle itself, where from 00:15:47.082 --> 00:15:49.078 the get go, because of 00:15:49.078 --> 00:15:51.087 abnormal genetic endowment 00:15:51.087 --> 00:15:52.046 00:15:52.046 --> 00:15:53.085 the heart is 00:15:53.085 --> 00:15:56.003 made wrong. Here's an example 00:15:56.003 --> 00:16:00.021 of something we call hypertrophic cardiomyopathy. 00:16:00.021 --> 00:16:06.012 Cardiomyopathy means heart muscle disease. 00:16:06.012 --> 00:16:09.083 This particular heart was immensely hypertrophic, you can see that left ventricle 00:16:09.083 --> 00:16:11.086 it's really tremendous with no 00:16:11.086 --> 00:16:14.009 valve disease, no hypertension to explain that, 00:16:14.009 --> 00:16:17.001 but look at the 00:16:17.001 --> 00:16:19.063 goofy muscle, you know 00:16:19.063 --> 00:16:23.031 what myocardium is supposed to look like, and the histology people never show you 00:16:23.031 --> 00:16:24.001 the kind of 00:16:24.001 --> 00:16:27.055 disarray and criss-crossing of fibers like that. 00:16:27.055 --> 00:16:33.056 This is the result of the genetic abnormality of this myocardium. 00:16:33.056 --> 00:16:37.004 All right, these are just a few examples of the things that can go wrong 00:16:37.004 --> 00:16:40.013 00:16:40.013 --> 00:16:41.093 and most frequently, 00:16:41.093 --> 00:16:46.000 if I had to pick from this whole list, I'd say hypertension and 00:16:46.000 --> 00:16:47.062 ischemic disease 00:16:47.062 --> 00:16:52.062 are the big actors at least in our population. 00:16:52.062 --> 00:16:55.052 Whatever the cause, as the heart is 00:16:55.052 --> 00:16:56.086 overburdened, 00:16:56.086 --> 00:17:00.005 there are certain compensatory mechanisms that kick in 00:17:00.005 --> 00:17:02.091 for a while, in other words, enable the heart to keep up 00:17:02.091 --> 00:17:05.042 with the abnormal strain, 00:17:05.042 --> 00:17:08.077 and some of these you know about, you've heard about I'm sure about the Frank Starling 00:17:08.077 --> 00:17:10.179 mechanism, 00:17:10.179 --> 00:17:11.000 00:17:11.000 --> 00:17:11.066 00:17:11.066 --> 00:17:17.005 where the myocyte is stretched by increased filling pressure, it's stretched 00:17:17.005 --> 00:17:19.002 and contracts then 00:17:19.002 --> 00:17:20.094 with greater vigor, 00:17:20.094 --> 00:17:23.429 in other words, it can put out more UMPH 00:17:23.429 --> 00:17:27.069 if it starts from a slight stretch. The trouble with that mechanism is that it fails. 00:17:27.069 --> 00:17:28.209 In other words, for a while 00:17:28.209 --> 00:17:31.085 it's adaptive, you get more and more UMPH for each 00:17:31.085 --> 00:17:34.017 contraction and then it peters out 00:17:34.017 --> 00:17:37.003 for a variety of reasons. 00:17:37.003 --> 00:17:40.039 A second compensation is hypertrophy, 00:17:40.039 --> 00:17:44.049 and you know about this, we talked about it last summer I guess. 00:17:44.049 --> 00:17:46.159 It's a situation where the same number 00:17:46.159 --> 00:17:49.149 of muscle cells are there 00:17:49.149 --> 00:17:51.071 but more sarcomeres are added 00:17:51.071 --> 00:17:54.089 and the muscle cells enlarge the whole 00:17:54.089 --> 00:17:56.074 tissue grossly 00:17:56.074 --> 00:17:59.001 enlarges and there's more UMPH. 00:17:59.001 --> 00:18:00.089 I mean it's very definitely 00:18:00.089 --> 00:18:03.097 a compensatory mechanism. 00:18:03.097 --> 00:18:05.001 A third compensation 00:18:05.001 --> 00:18:08.023 mechanism I've listed 00:18:08.023 --> 00:18:11.061 is activation of neuro-humoral systems and we're not going to go into that 00:18:11.061 --> 00:18:13.649 in much detail, just enough detail 00:18:13.649 --> 00:18:15.002 so you know that 00:18:15.002 --> 00:18:17.006 they are there. 00:18:17.006 --> 00:18:19.083 Now here's hypertrophy! 00:18:19.083 --> 00:18:22.051 Normal size myocytes you see over here 00:18:22.051 --> 00:18:25.092 and each one is on the average just a little bit thicker 00:18:25.092 --> 00:18:27.007 than the normal 00:18:27.007 --> 00:18:28.038 00:18:28.038 --> 00:18:32.051 That's because of addition of sarcomeres, not much change in the number of cells 00:18:32.051 --> 00:18:36.005 and you can imagine these cells having more UMPH like a weight lifter, 00:18:36.005 --> 00:18:41.095 imagine that, like a weight lifters arm 00:18:41.095 --> 00:18:44.389 This is maybe what we see 00:18:44.389 --> 00:18:48.789 grossly, there's an increase in the muscle, increase in the weight of the heart, 00:18:48.789 --> 00:18:49.071 and sometimes 00:18:49.071 --> 00:18:53.093 we see concentric hypertrophy, meaning 00:18:53.093 --> 00:18:58.039 the chamber is not enlarged, it may even be a little smaller, gross thickening of the walls 00:18:58.039 --> 00:18:59.098 and its 00:18:59.098 --> 00:19:00.077 concentric. 00:19:00.077 --> 00:19:03.048 We see that usually with pressure overload. 00:19:03.048 --> 00:19:06.039 With a volume overload, we may see 00:19:06.039 --> 00:19:07.052 what looks like no hypertrophy 00:19:07.052 --> 00:19:10.058 at all except that's a lot more muscle 00:19:10.058 --> 00:19:13.046 than there is normal, it's just that it's dilated. 00:19:13.046 --> 00:19:16.015 That also happens in very advanced failure 00:19:16.015 --> 00:19:19.005 from any cause, you see this sort of eccentric picture. 00:19:19.005 --> 00:19:20.038 00:19:20.038 --> 00:19:24.009 When it comes to the neuro-humoral mechanisms, I'm just going to race through these now, 00:19:24.009 --> 00:19:25.053 there is 00:19:25.053 --> 00:19:28.021 first of all 00:19:28.021 --> 00:19:30.001 00:19:30.001 --> 00:19:32.077 all of these things tend to be triggered by pressure and 00:19:32.077 --> 00:19:36.409 stretch receptors that are scattered through the heart 00:19:36.409 --> 00:19:38.789 the aorta, the carotids, 00:19:38.789 --> 00:19:41.031 and the kidney even there is such sensing. 00:19:41.031 --> 00:19:45.074 When the cardiac output begins to drop, these receptors say UH OH 00:19:45.074 --> 00:19:50.015 and they trigger a number of things, one of the things they trigger is 00:19:50.015 --> 00:19:51.093 a central nervous system, 00:19:51.093 --> 00:19:54.035 i'm sorry, the sympathetic nervous system 00:19:54.035 --> 00:19:57.559 with release of norepinephrine 00:19:57.559 --> 00:19:59.005 and this can produce 00:19:59.005 --> 00:20:02.056 a contractile boost for the heart 00:20:02.056 --> 00:20:04.029 00:20:04.029 --> 00:20:07.086 this can produce an increased heart rate 00:20:07.086 --> 00:20:11.094 these things will help meet an abnormal load 00:20:11.094 --> 00:20:16.005 and also this will produce vasoconstriction peripherally. 00:20:16.005 --> 00:20:18.061 This is designed, 00:20:18.061 --> 00:20:20.053 this evolved this way presumably to 00:20:20.053 --> 00:20:26.006 to make sure that blood gets shunted to essential organs 00:20:26.006 --> 00:20:29.026 so there's peripheral vasoconstriction 00:20:29.026 --> 00:20:33.549 which increase, well we'll talk about what the bad things it does. 00:20:33.549 --> 00:20:35.219 Vasopressin is released 00:20:35.219 --> 00:20:38.091 from the hypothalamus, that's also a vasoconstrictor, 00:20:38.091 --> 00:20:41.017 and we talked in class previously about 00:20:41.017 --> 00:20:44.092 the renin-angiotension-aldosterone system. 00:20:44.092 --> 00:20:45.095 00:20:45.095 --> 00:20:51.549 The kidney senses the decreased flow that's coming to it, secretes renin which 00:20:51.549 --> 00:20:56.005 acts on angiotensinogen which is circulating protein 00:20:56.005 --> 00:20:56.095 00:20:56.095 --> 00:20:58.093 forms angiotensin I 00:20:58.093 --> 00:21:02.004 and then there's angiotensin converting enzyme which takes angiotensin II 00:21:02.004 --> 00:21:03.038 that in turn 00:21:03.038 --> 00:21:05.001 stimulates the production 00:21:05.001 --> 00:21:10.018 in the adrenals of aldosterone. 00:21:10.018 --> 00:21:11.005 00:21:11.005 --> 00:21:14.859 The importance of all of this is first of all angiotensin II 00:21:14.859 --> 00:21:18.064 is also a vasoconstrictor 00:21:18.064 --> 00:21:20.047 and 00:21:20.047 --> 00:21:24.083 between angiotensin II and aldosterone, there is 00:21:24.083 --> 00:21:29.038 sodium retention, salt retention, sodium retention and water retention 00:21:29.038 --> 00:21:30.067 and that has 00:21:30.067 --> 00:21:33.083 some important consequences. 00:21:33.083 --> 00:21:38.061 I just listed, I don't have time to go into it, the natriuretic peptides 00:21:38.061 --> 00:21:42.085 secreted by the heart which tend to counteract the renin-angiotensin-aldosterone 00:21:42.085 --> 00:21:45.087 system to some extent. 00:21:45.087 --> 00:21:49.058 Unfortunately, all of these 00:21:49.058 --> 00:21:52.036 mechanisms 00:21:52.036 --> 00:21:56.000 are limited in how much help they can provide and there's a downside 00:21:56.000 --> 00:21:57.033 to a lot of them. 00:21:57.033 --> 00:21:58.069 Now 00:21:58.069 --> 00:22:02.028 problems with hypertrophy, it just gets bigger and 00:22:02.028 --> 00:22:04.004 bigger and bigger muscle, 00:22:04.004 --> 00:22:08.051 it doesn't work out that way because the capillary network in the muscle 00:22:08.051 --> 00:22:11.269 does not increase in parallel and you 00:22:11.269 --> 00:22:15.259 end up with perfusion problems so there's a limit to how much hypertrophy 00:22:15.259 --> 00:22:18.039 the tissue can stand. 00:22:18.039 --> 00:22:21.064 Same is true for the ratio between mitochondria and 00:22:21.064 --> 00:22:27.033 and contractile protein, so to speak, the mitochondria-to-meat ratio 00:22:27.033 --> 00:22:31.038 does not keep up to what it should be so the energy is a problem. 00:22:31.038 --> 00:22:33.044 Then very importantly 00:22:33.044 --> 00:22:38.066 we're learning that there is altered gene expression 00:22:38.066 --> 00:22:40.038 and alteration in the 00:22:40.038 --> 00:22:43.073 proteins that are produced, and these may involve 00:22:43.073 --> 00:22:45.669 contractile proteins, 00:22:45.669 --> 00:22:46.068 segmentation 00:22:46.068 --> 00:22:50.071 contraction coupling them, they may involve energy utilization, 00:22:50.071 --> 00:22:53.088 but some abnormal proteins are made 00:22:53.088 --> 00:22:57.053 there's an increase in apoptosis 00:22:57.053 --> 00:23:00.003 in a hypertrophic myocardium 00:23:00.003 --> 00:23:01.519 and, under the influence 00:23:01.519 --> 00:23:06.969 of all of this is actually driven by the various hormonal 00:23:06.969 --> 00:23:09.098 things that i've mentioned 00:23:09.098 --> 00:23:11.469 and with something 00:23:11.469 --> 00:23:15.095 we call remodeling occurs, there's a change in geometry of the ventricle 00:23:15.095 --> 00:23:19.083 which can have implications of tugs on the chordae tendinae of the mitral valve 00:23:19.083 --> 00:23:23.007 the wrong valve, you can get mitral regurgitation, 00:23:23.007 --> 00:23:26.023 it's a disadvantageous thing 00:23:26.023 --> 00:23:30.002 often associated with a lot of fibrosis, that blue-green tissue racing through the myocardium 00:23:30.002 --> 00:23:31.045 00:23:31.045 --> 00:23:35.001 is a fibrosis in the remodeled ventricle 00:23:35.001 --> 00:23:39.011 which causes problems of its own as you can imagine, I don't have to go into any detail 00:23:39.011 --> 00:23:40.015 00:23:40.015 --> 00:23:42.084 So that's a problem 00:23:42.084 --> 00:23:44.078 and there's a problem 00:23:44.078 --> 00:23:48.091 with neurohumoral activation, 00:23:48.091 --> 00:23:50.082 vasoconstriction increases the 00:23:50.082 --> 00:23:54.084 afterload that this poor old failing heart has to pump against. 00:23:54.084 --> 00:23:56.022 It sounds like 00:23:56.022 --> 00:23:59.003 a nice mechanism, but it 00:23:59.003 --> 00:24:00.026 bites the heart 00:24:00.026 --> 00:24:04.072 Various of these humoral substances are 00:24:04.072 --> 00:24:06.001 cardiotoxic 00:24:06.001 --> 00:24:07.028 chronically 00:24:07.028 --> 00:24:09.095 in other words, they are responsible for the increase in apoptosis 00:24:09.095 --> 00:24:14.066 they drive the remodeling and it's a bad thing for the heart 00:24:14.066 --> 00:24:16.003 in the long run, 00:24:16.003 --> 00:24:17.209 and we know about the 00:24:17.209 --> 00:24:21.529 implications of sodium and water retention and how that 00:24:21.529 --> 00:24:24.041 overloads the heart. 00:24:24.041 --> 00:24:26.026 All of these things 00:24:26.026 --> 00:24:26.069 contribute to the downward spiral 00:24:26.069 --> 00:24:29.071 00:24:29.071 --> 00:24:33.052 and I've simplified a very complex business, but 00:24:33.052 --> 00:24:35.016 there are many 00:24:35.016 --> 00:24:38.053 consequences for the peripheral tissues and that's what we're 00:24:38.053 --> 00:24:41.859 really talking about when we talk about heart failure, what's going on 00:24:41.859 --> 00:24:44.299 in the peripheral tissues. 00:24:44.299 --> 00:24:48.007 These consequences we can talk about in a number of ways, we talk 00:24:48.007 --> 00:24:51.058 about sometimes forward failure and backward failure. 00:24:51.058 --> 00:24:53.509 Forward failure being the idea that 00:24:53.509 --> 00:24:58.066 the failing heart does not perfuse the tissues well enough, and 00:24:58.066 --> 00:24:59.669 backward failure you're familiar 00:24:59.669 --> 00:25:03.036 with the idea of passive congestion and we talked about that in class 00:25:03.036 --> 00:25:05.072 so you have a good image of that. 00:25:05.072 --> 00:25:08.929 We speak of left heart failure and right heart failure, 00:25:08.929 --> 00:25:10.028 most processes that cause 00:25:10.028 --> 00:25:12.002 heart failure start out on the left 00:25:12.002 --> 00:25:15.005 but it's a closed plumbing system 00:25:15.005 --> 00:25:20.008 so as the left heart fails, the right heart is going to fail. 00:25:20.008 --> 00:25:21.034 The commonest 00:25:21.034 --> 00:25:25.099 cause of right heart failure then is left heart failure. 00:25:25.099 --> 00:25:29.052 There are some of the examples where the right heart fails primarily and it has to do 00:25:29.052 --> 00:25:31.035 with things happening in the lungs, 00:25:31.035 --> 00:25:37.015 they're relatively less common and you'll hear more about them some other time, 00:25:37.015 --> 00:25:41.043 but the backward consequences of left and right heart failure are very 00:25:41.043 --> 00:25:45.076 familiar to you already, we know that when the left heart fails you get 00:25:45.076 --> 00:25:47.509 pulmonary congestion and edema, 00:25:47.509 --> 00:25:50.053 when the right heart fails, you get 00:25:50.053 --> 00:25:52.066 elevation of hydrostatic 00:25:52.066 --> 00:25:55.034 pressure in a variety of tissues 00:25:55.034 --> 00:25:56.419 with associated 00:25:56.419 --> 00:26:00.389 congestive changes in organs and accumulation of edema 00:26:00.389 --> 00:26:02.007 fluid and this 00:26:02.007 --> 00:26:05.002 is when we start to speak of congestive heart failure. 00:26:05.002 --> 00:26:08.063 We're throwing that adjective very frequently 00:26:08.063 --> 00:26:10.019 00:26:10.019 --> 00:26:14.019 What we're not emphasizing, and I'll just conclude by mentioning this, 00:26:14.019 --> 00:26:15.083 are the forward changes 00:26:15.083 --> 00:26:18.084 associated with left heart failure, in other words, when the left 00:26:18.084 --> 00:26:20.099 heart fails, things begin to 00:26:20.099 --> 00:26:25.559 happen because tissues in a variety of places simply aren't being perfused. 00:26:25.559 --> 00:26:27.027 And you're familiar already with 00:26:27.027 --> 00:26:30.091 the activation of the 00:26:30.091 --> 00:26:32.062 renin-angiotensin-aldosterone system 00:26:32.062 --> 00:26:37.025 from forward failure to 00:26:37.025 --> 00:26:39.099 supply enough blood to the kidney, 00:26:39.099 --> 00:26:45.269 I would point out that as the perfusion drops more and more, 00:26:45.269 --> 00:26:49.096 the kidney can really shut down as far as its excretory function and nitrogenous 00:26:49.096 --> 00:26:52.086 waste can pile up. 00:26:52.086 --> 00:26:54.042 Sometimes they speak, 00:26:54.042 --> 00:26:58.036 people speak, of a cardio-renal syndrome because of this. 00:26:58.036 --> 00:26:59.054 Well many other 00:26:59.054 --> 00:27:04.079 tissues suffer from this lack of perfusion in the same way. 00:27:04.079 --> 00:27:07.075 We've shown you for instance the liver, 00:27:07.075 --> 00:27:11.006 and the liver gets caught in a one-two punch, 00:27:11.006 --> 00:27:12.919 there's resistance to outflow from the liver 00:27:12.919 --> 00:27:16.004 the fact is that the poor old failing left ventricle isn't delivering enough blood 00:27:16.004 --> 00:27:17.002 to this, the central 00:27:17.002 --> 00:27:19.077 lobular area, 00:27:19.077 --> 00:27:22.000 and it undergoes a sort of hemorrhagic 00:27:22.000 --> 00:27:24.007 necrosis which you remember that, you never forget 00:27:24.007 --> 00:27:26.081 that kind of a picture. 00:27:26.081 --> 00:27:31.014 Now something, a little wrinkle that I'll point out here, 00:27:31.014 --> 00:27:31.085 is that the aldosterone 00:27:31.085 --> 00:27:35.309 levels in patients in failure are way way up there 00:27:35.309 --> 00:27:36.096 and part of it 00:27:36.096 --> 00:27:40.023 obviously is because it's been triggered by the production of angiotensin II 00:27:40.023 --> 00:27:42.054 and so forth, but the liver 00:27:42.054 --> 00:27:44.083 when it's in that kind of a state, 00:27:44.083 --> 00:27:48.084 does not catabolize aldosterone the way it should, 00:27:48.084 --> 00:27:52.559 and the patient may end up with a twenty fold increase in aldosterone level partly because 00:27:52.559 --> 00:27:55.041 of synthesis and partly because of 00:27:55.041 --> 00:27:57.033 "non tearing down" 00:27:57.033 --> 00:27:58.063 00:27:58.063 --> 00:27:59.053 by the liver 00:27:59.053 --> 00:28:01.011 00:28:01.011 --> 00:28:02.041 One more example, the gut 00:28:02.041 --> 00:28:04.053 may suffer in very advanced cardiac 00:28:04.053 --> 00:28:06.519 failure, patches of mucosa 00:28:06.519 --> 00:28:09.003 in the bowel may undergo 00:28:09.003 --> 00:28:13.011 necrosis because they're furthest from the blood supply 00:28:13.011 --> 00:28:17.005 and we speak of ischemic colitis, a bit of a misnomer as it is an inflammatory condition, 00:28:17.005 --> 00:28:17.097 00:28:17.097 --> 00:28:18.096 but actually that sort of thing 00:28:18.096 --> 00:28:21.047 can be a problem. 00:28:21.047 --> 00:28:24.929 Other organs and in fact even the central nervous system in very advanced failure 00:28:24.929 --> 00:28:26.018 we see problems 00:28:26.018 --> 00:28:29.002 with CNS function. 00:28:29.002 --> 00:28:32.051 Well I turn the baton over 00:28:32.051 --> 00:28:34.259 to Dr. Matthews 00:28:34.259 --> 00:28:38.012 you just keep some of these images in mind and she will flesh them out, 00:28:38.012 --> 00:28:38.072 00:28:38.072 --> 00:28:40.085 as they say, with the clinical realities 00:28:40.085 --> 00:28:43.031 and with some of the 00:28:43.031 --> 00:28:44.084 therapeutic strategies 00:28:44.084 --> 99:59:59.999 that make sense I hope.