Good morning. I'm pleased to be joining you today for the master class in cardiovascular physiology. My name is Lakshmi Sridharan, and I'm joining you from Emory University. Today we will be discussing the hemodynamic assessment of diastolic function. I have no relevant financial disclosures. Here's our roadmap for today. Let's first define what left ventricular diastology is and why we care about it in the critical care setting. And finally, a practical assessment at the bedside for diastolic function in the non-cardiology setting and some of the esoteric things that cardiologists and echocardiographers look at when assessing diastology. Of note, we will not be discussing right ventricular diastology today. Let's begin by looking at normal left ventricular diastology. On the graphic on the left-hand side of the screen, you see LV diastole denoted. And LV diastole begins at the end of the T wave until the start of the subsequent QRS complex. On the graphic, you see four phases of diastole noted. And this occurs between aortic valve closure and subsequent mitral valve closure. So there are four phases denoted here. The first is isovolumic relaxation during which the LV is not filling. Nevertheless, the isovolumic relaxation period is actually an active ATP-dependent process during which there is an untwisting of the left ventricle and a pressure gradient begins to form from the apex to the base of the LV. And this causes a suction-like effect that pulls blood from the LA to the LV during the second phase of diastole called early rapid filling. This corresponds to the classic mitral inflow E wave that we here discussed and that is shown on the graphic. During this period of time, the LV is filling quickly due to the pressure gradient between the LA and the LV until the third phase of diastole during diastasis when there is an equilibration of pressures between the two chambers. And then the LV doesn't really fill again until atrial contraction. Throughout all of this, normal diastology can be considered to be an adequate filling of the left ventricle without a pathologic increase in left atrial filling pressures. And this needs to occur both at rest and during exercise or during any process such as illness when an increased cardiac output might be required. So given that that's normal LV diastology, what is LV diastolic dysfunction? Well, for starters, diastolic dysfunction is not just HEF-PEF or heart failure with preserved EF. In fact, diastolic dysfunction is very common in the population. And in recent studies in the United States, about a third of adults over the age of 45 probably have some amount of diastolic dysfunction. Notably, all systolic dysfunction comes with at least some degree of diastolic dysfunction. But the extent of diastolic dysfunction is not determined by simply the amount of systolic dysfunction alone. Diastolic dysfunction is a strong predictor of mortality. And you can see why when you look at the risk factors on the right-hand side of the screen. All of those risk factors would be risk factors for mortality and morbidity in any of your ICU patients, including advanced age, long-standing hypertension, a body habitus that might lead to obesity or obstructive sleep apnea, and more and more commonly these days, diabetes. So here we're looking at the pressure volume loop of the left ventricle in a normal heart and in a heart with diastolic dysfunction, where you see that the EDPVR curve shifts upwards with elevated diastolic pressures. This is as a result of two of the most important hemodynamic derangements that happen with diastolic dysfunction, the first of which is a decrease in LV compliance, or what we call a stiff chamber. And the second of which is a decrease in LV rate of relaxation. So essentially, this is what we call tau, or the rate of myocardial relaxation that begins during isovolumic relaxation. And it looks at the LV systolic pressure decay. And hemodynamically, the fall of LV pressure is a marker for myocardial relaxation. And it is an important rate that we look at to determine if LA pressures will subsequently rise. So these are the two most important properties, again, of diastolic dysfunction. As a result of these two properties, you can have a decrease in left ventricular filling, which can also lead to a change in LV geometry, such as LV concentric hypertrophy or eccentric hypertrophy, and an increase in left heart filling pressures from the ventricle to the atrium and then backing up into the pulmonary venous system. Under these circumstances, small physiologic stressors, such as an increase in volume or a requirement for a change in cardiac output, for example, if a patient is sick with a routine illness or something more profound like sepsis, everything will worsen hemodynamically and the patient will become symptomatic as a result of their diastolic dysfunction. So the key hemodynamic abnormalities from diastolic dysfunction that affect ICU patients primarily are the increase in left atrial pressures, and then the increase really in the LV and diastolic pressure, which means an increase in pulmonary capillary wedge pressure in most situations. Again, as a reminder, the LA pressure has at this point increased to maintain adequate filling of the left ventricle, and once you have increased pulmonary capillary wedge pressures and a backup of the pressure gradient into the venous system of the pulmonary vascular bed, we are now very concerned about pulmonary congestion and flash pulmonary edema. So what are the factors we can control in the ICU that may exacerbate diastolic dysfunction? Well, heart rate is certainly one of them because the rate of someone's heart affects diastole. Afterload, whether it be just like blood pressure or more subtly systemic vascular resistance, which can be quite high in patients with lower blood pressures in the context of systolic dysfunction, and then preload. So in patients with advanced diastolic dysfunction, left heart filling pressures may need to be relatively elevated in order to maintain blood pressures and cardiac output. And this is in part due to changes in the coronary perfusion pressure. And by this I mean, for example, in patients with advanced coronary artery disease who do have diastolic dysfunction, the coronaries may already be maximally vasodilated. And as you know, coronary perfusion pressure is really estimated by the difference between diastolic blood pressure and LVEDP. And so as diastolic dysfunction worsens in patients who have advanced coronary artery disease, the LVEDP will go up and the delta between the diastolic blood pressure and LV filling pressures will decrease. So the clinical implications of diastolic dysfunction in critically ill patients can be profound as a result of the increase in LV and diastolic pressure. So in mechanically ventilated patients, this can lead to significant alterations of gas exchange and meaning failure for mechanical ventilation. In fact, in non-cardiac illness such as sepsis, fluid management can become a lot more challenging, particularly in the later phases of sepsis when diuresis may become more important. Management of pulmonary hypertension, particularly in groups 1, 3, and 4, pulmonary hypertension can become confounded if patients have diastolic dysfunction as this will demonstrate an increase in left atrial filling pressures. And then we have to be pretty clear on the difference of what is contributing to pulmonary pressure escalation, whether it's diastology or an alternate form of pH. We know that independent of a low EF, diastolic dysfunction causes morbidity after non-cardiac surgery, including an increased length of stay in the ICU setting. So let's take a look at a practical approach. Let's look at a case that might roll into your ICU and how you would measure LV diastology and left heart filling pressures. So here we have a woman. She's 70 years old. She's got a past medical history of poorly controlled hypertension and an NSTEMI in 2018. She's admitted to your ICU. She's hypoxic and has severe hypertension with a blood pressure of 180 over 105. You see some of the bedside POCUS images that you and your team, excellent POCUS images by the way, have gotten. And the question you have is, is her diastology normal or abnormal and how does it affect your management? And you see that her LVEF is not perfect, but it's near normal. Her left atrium looks pretty big. Her LV septum looks pretty thick. In fact, there it's measured to be 1.7 centimeters. And in panel B, you see that she has significant tricuspid regurgitation. On continuous wave Doppler, her TR jet is 3.3 meters per second, which is high. We typically estimate anything over 2.8 meters per second to be a binary cut point for an indicator of diastolic dysfunction. And in her case, estimates out to a pulmonary artery systolic pressure somewhere between 44 to maybe 50, depending on what you estimate her right atrial pressure to be. So she's got a lot of risk factors for diastolic dysfunction just off the bat. For one thing, her septum is thick, suggesting that her LV has been facing high afterload for a long time. Her left atrium is large, suggesting that the left atrium has been dealing with high pressures for a long time. And her TR jet is elevated, suggesting increased pulmonary pressures. So when you're doing a bedside ultrasound or POCUS exam in the ICU in a patient like this, can you measure diastology and what is the goal of that for you? And I would argue that your goal is to estimate left heart filling pressures to help you guide management in the absence of a PA catheter or a SWAN GANS catheter. And here are a couple bedside things to think about that can help guide you in the right direction. First, look at whether you think this EF is normal or not normal. And if it is normal, if the EF is greater than 50%, is there evidence of myocardial disease? Are all the walls moving properly? Is the septum abnormally thick, etc.? How thick is that septum? I've given you some approximate normals there. When the septum is profoundly thicker than normal, you need to start thinking about LV myocardial disease being present. Does the left atrium look very large? And how bad is the TR? You can look at it on color Doppler and measure it on continuous wave Doppler. If two out of four of these seem positive to you at bedside, you're possibly dealing with high left heart pressures. But if three or more are positive on a bedside POCUS, you're more than likely dealing with elevated left heart pressures. And getting a formal echocardiogram to assess those filling pressures becomes more important. So back to our case, we've got the 70-year-old woman coming to you with essentially hypertensive urgency, emergency, and pulmonary edema. And right off the bat, you know that though her EF is near normal, she's got myocardial disease given her history of endostomy and her thick septum. Her atrium is large and she's got a significant amount of tricuspid regurgitation. So she likely has abnormal diastology. And more relevant for you in that moment, she likely has elevated left heart filling pressures, meaning her risk of flash pulmonary edema is very high. And you do need to think about upfront diuresis, but know that the challenge of maintaining diuresis without causing renal dysfunction may be significant. So when you approach abnormal diastology in the ICU, for example, in our case, what are the management implications? To begin with, when you have a patient with advanced diastolic dysfunction, there's going to be greater coupled ventricular arterial stiffening. So with the stiffening of the LV chamber, the arterial system will also be significantly more stiff. And as a result of that, finding a sustainable antihypertensive strategy that won't cause hypotension can be challenging. Upfront, the patient may be hypervolemic given the flash pulmonary edema, but you will actually have a quite narrow window for euvolemia, after which you might start to develop significant renal dysfunction. In this case, physical exam may not be quite reliable, particularly if the right heart does not suffer from the same issues and filling pressures that the left heart is suffering from. The importance of things like dietary sodium and limiting that even in the ICU can be significant. Anything that could derange volume status or increase blood pressure. You have to think about CAD risk management, particularly in the context of what we discussed with patients who may already have maximally dilated coronary vessels. And once the patient becomes euvolemic and you have control of their blood pressure, there's a lot of utility in tracking diastology formally on echocardiogram, because if the patient does have some improvement or reversal of diastolic dysfunction, that actually portends for better long-term outcomes. And finally, though this patient may have come to your ICU for management of hypertensive urgency and flash pulmonary edema, if they have significant diastolic dysfunction, this patient could be a prime candidate for cardiology referral for CardioMEMS, which is a device placed in the main PA artery to measure pulmonary pressures continuously as an outpatient and track and alert patients to when they need to take more diuretics and presumably keep them out of the hospital. When you're thinking about formally quantitating LD diastology, this is where we start to think about the mitral E and A waves that we touched on briefly at the start of our discussion. And in this case, we're looking at the mitral inflow. So we have our sample volume on echo at the mitral valve. Here you see that the E wave is the peak mitral flow velocity that occurs in early diastole. The A wave is the peak mitral flow velocity at atrial contraction, or that fourth phase of diastole that we saw on our early slides. We can see the mitral deceleration time and the left ventricular isovolumic relaxation time denoted as LVIRT. Here we see the different mitral inflow filling patterns that suggest different types of LV diastology. On the far left, you have a normal pattern where E is greater than A. And then when you get to grade one, you have impaired relaxation where the A, the atrial contraction wave, is actually higher than the E. At this point, there is a change in the LV rate of relaxation. So the LV is not relaxing quite as quickly as it needs to, but LV compliance hasn't changed yet. So left atrial pressures are still normal. As you progress to grade two diastolic dysfunction in a pseudonormal pattern, LV compliance has now decreased and left atrial filling pressures is now increasing. And when you finally get to a restrictive mitral inflow pattern, LV compliance is so low that left heart filling pressures are quite high and are very difficult to reverse. More formally, when you look at a heart which has a normal LVEF and no myocardial disease, and the definition of myocardial disease is on the right-hand side of the screen. So for example, no wall motion abnormalities or pathologic hypertrophy of the LV, then you can use this criteria. And there are four criteria at the top. And you see the septal E-prime and lateral E-prime we get from the tissue Doppler imaging on echocardiogram. But you also see that we look at the tricuspid regurgitant jet, which we mentioned earlier, and the left atrial volume index. And we use 34 milliliters per meter squared as a rough binary cutoff for when the left atrium is enlarged. And when two or more of these criteria are present, we consider diastolic dysfunction to be present, even in the context of a normal EF and no myocardial disease. Here, we look at the formal algorithm for quantitating LV diastology for patients with a low EF or with patients who have any type of myocardial disease. On the far left-hand side of the screen, we see that when the A wave is a lot bigger than the E wave, so that's going to be grade one diastolic dysfunction, where left heart filling pressures, left atrial pressures are still normal, but the rate of relaxation of the LV myocardium has decreased. By the time you get to the far right-hand side of the screen and grade three diastolic dysfunction, we have a restrictive mitral inflow filling pattern, the E wave is very high, and left atrial pressures are now concordantly very, very high. So our key learning points when assessing diastolic function in the ICU. Number one, the two most important changes in diastolic dysfunction we have to look at first, the decreased rate of relaxation of the left ventricle, and second, the decreased compliance of the left ventricle. These two things lead to all the subsequent hemodynamic changes that affect your management at the bedside. Diastology varies with loading conditions. This means that in some patients, the extent of diastolic dysfunction can improve if they are volume optimized and their afterload is optimized. Elevated filling pressures of the left heart can exist in the context of normal diastolic function, so in a patient who is undergoing abnormal stressors. Systolic dysfunction always, always brings with it some amount of diastolic dysfunction, but the extent of which is not directly predictive from the degree of systolic dysfunction. And diastolic dysfunction in normal EF patients requires very thoughtful management of volume, vascular stiffness, and certainly also heart rhythm. Happy to take any questions you may have.

cardiovascular physiology

hemodynamic assessment

diastolic function

left ventricular diastology

diastolic dysfunction

hemodynamic abnormalities