Dr. J. Thomas Heywood discusses the prevalence of heart failure and pulmonary hypertension in women while reviewing new treatment options resulting from pharmacological studies.
It is my pleasure and honor to introduce Dr Heywood who probably does not require introduction but I will do so anyway. So a lot of people locally and probably nationally are familiar with Dr Heywood who joined scripts clinic in 2005 to serve as director of the heart failure and recovery program. And he's obviously um I'm supposed to read this but I'm going to tell you just he's been instrumental in the development of our L. VAD program. Really taken that to new heights um for people who are here. He's really grown the heart failure program, it's really, really been a pleasure to learn from him and work with him. Um in 2012 he became the director of the L. VAD left ventricular assist device program here. Um and that's really taken off with large numbers. He is internationally recognized as an expert in heart failure. He's had over 80 publications, lectured throughout the world on cardiomyopathy. He published the cardio renal syndrome book, which I do think is on my bookshelf behind us. We've all had a chance to read. That's been extremely helpful. We were able to steal him from Loma linda and he's been instrumental here at Scripps Clinic. So I will turn it over to Dr Heywood who will wrap up finishing along the lines of cardiomyopathy and specifically pulmonary hypertension, all of these issues that are far more prevalent in women. Of course, important in men as well. Thank you. Dr Heywood for joining us this morning as a theme of this is that women and cardiovascular disease. Unfortunately, when women have been unrepresented in trials, yet more women than men have pulmonary hypertension have have path and this life saving diagnosis is often delayed for years in women and this causes unnecessary morbidity and mortality in them. So, what I'm going to focus on today is some of the new treatments for these diseases. Once you make the diagnosis and show you why this diagnosis is so important because we can treat these so well Now, even for heart failure with low ejection fraction, which affects women, not quite as often as men. But certainly millions of women have low ef heart failure in the United States. One of the most important new drugs now, about five years old is the cooper drill val certain or interest. Oh, this was compared to val Certain in the paradigm trial. This is actually two drugs. It has the old drug that we know of as val start in which is an A. R. B. And so cooper trill, which blocks knepper listen, by blocking nepalese and this causes vessel dilation, lower blood pressure, reduce sympathetic tone and also causes a natural reasons. So patients tend to diaries with uh cooper trove out starting more than they would just do with other agents. This trial handsomely met its end point with an 80 reduction in heart failure, hospitalizations and cardiovascular death. And it even reduced all cause mortality, which is very rare. There are contraindications. We can't use wrasse blockers and pregnancy. Any history of angina Dema that swelling of the lips or tongue with ace inhibitors. You can't use it. You don't use it with an ace. You don't need it, but you have to stop an ace inhibitor for two days prior to using this. Patients with low blood pressure are not good candidates for this. What about patients with acute heart failure in the hospital? This was a pioneer trial giving the drug to patients. You can see women underrepresented again. About a quarter of the trial. This was well represented with african americans, fortunately. And The benefit of this was that eight weeks is that the patients were re hospitalized at eight weeks, only eight got sick, cooper travel certain versus 14% that got an al april. So you cut re hospitalization for heart failure about in half by starting c cooper travel, starting in the hospital. So we tried to do this Most of the time in our hospitalized patients with EFF less than 40%. So what about patients that have a normal ejection fraction? This was the paragon trial and unfortunately this was not as positive. So it didn't quite read reach its end point. Have Pep is a difficult disease. There's probably a lot of of genotype differences in the disease. Patients with CFS of 45 are lumped together with patients with CF of 85%. But what they found was that especially in women, there was a 27% reduction in heart failure, hospitalization, And especially those with less than 57%. So the FDA has approved has voted to approve the use of this drug for those with the EFS less than about 55% especially in women. And then works best have started in patients that have been recently being hospitalized within the last 30 days. So we have had some we can use this drug in some patients with increased ejection fraction. And this has reached the guidelines in 2016, patients with reduced EF Either you should switch them or use this as initial therapy. So cooper travel certain is really replacing ace inhibitors and arbs for most patients with low ejection fraction, as long as they don't have terrible renal function or blood pressure, less than 90 the other big drug that's uh is really quite important and everyone should know about. And I'm sure you do are the sodium glucose co transporter inhibitors, the SGL T two inhibitors. These were initially uh developed for diabetes. How they work is glucose is filtered in the glamorous realists and then re absorbed in the proximal tubules and it gets reabsorbed uh for the most part, you don't you know, you don't want to lose all your glucose in the urine by blocking this. Patients with diabetes lose glucose in their urine more than normal And they lose about 80 g of glucose a day, Which is about 300 calories a day. So patients tend to lose weight on these drugs. What makes them attractive is that they're one pill a day um lowers hemoglobin, a one c about as well as any pill. There's very little hypoglycemia. There's weight loss of 3 to 5% of body weight, lowers blood pressure. So these are very good agents for diabetes. But we found out that they had their effects extend way beyond those effects Justin diabetes. So they're okay diabetes drugs. But we looked at these in cardiovascular endpoints in the Emperor Greg trial, which is now about five years ago. And the reason we do this is that many drugs for diabetes actually worsen cardiovascular outcomes. What that wasn't the case with this agent. They actually had improved cardiovascular outcomes. They met their primary endpoint of heart attack, stroke and cardiovascular mortality. The major benefit was cardiovascular death was reduced by 38 and all cause mortality was reduced by 32%. And the surprising thing is that they reduced heart failure hospitalization as well. Maybe from this weight loss may be from the non this osmotic diaries is from glucose. But this was in people with coronary disease and diabetes. And this just shows you this profound effect that they have. So the next trial was the emperor reduced trial was looking at using this agent in people with heart failure, not necessarily with diabetes. So we're starting to use these agents in those patients without diabetes and they benefit renal function And they reduce renal transplant dialysis or drop in G. fr by 50%. So we don't have many drugs that improve renal outcome. And these are one of them. And with reduced ejection fraction we see a benefit not as good a benefit as in the Emperor Wreg trial because these patients didn't have coronary disease but typically flows in has been approved for heart failure. And um it's and uh Mbugua flows and will probably be approved this year. Now in terms of women, it's very important that you put a lot of glucose into your urine. And so there's an increased risk of yeast infections in women with these agents. So you need to warn them about that. Now, most women don't get yeast infections with these, but a number of them do. And uh usually typically easily treated but obviously an inconvenience. But On the opposite of the Yeast infection they might lose 3-5 of their body weight and their blood pressure goes down. So very typically we see although these aren't approved for weight loss, we typically see patients lose weight on these agents which patients uh enjoy. So tips for using these agents and heart failure. They're not for type one diabetics, not for G. F. Are less than 30. We talked about the East infection. Hypoglycemia is rare. We may need to reduce diuretics. Same thing with the Cupertino val certain may need to reduce diuretics in those patients as well. So if the patient comes back with lowest blood pressure, we would reduce the diuretic first in those patients. And I have many patients with heart failure now who don't need to take diuretics anymore once they're on these agents and they can be on C cooper travel certain and S. G. L. T two inhibitors, certainly at the same time. So the drugs now for heart failure are beta blockers, carvedilol Utopia Law sprung lac tone, S. G. L. T two inhibitors. And so cooper travel certain. So we have four typical drugs that we use with heart failure and then we use diuretics as we need to. So I'm going to end up with pulmonary hypertension. Uh pulmonary hypertension. You often see on echo. So if there's one message I would like to convey from this is that when you see a woman with shortness of breath or a man for that sake. When you order the echo, look beyond the ejection fraction and look to see if they have pulmonary hypertension. That's the biggest uh Marker that they're dysosmia is coming from their heart. If they have hype pressures anything about 40 or 50 of mercury on the Echo is abnormal and needs to be evaluated. Now there's two major types of pulmonary hypertension. There is pulmonary venous hypertension or post capillary pulmonary hypertension. This is caused by left heart disease. So low E. F. Have heart failure with normal ejection fraction mitral regurgitation, aortic stenosis. So it's often pretty easy to know why they have pulmonary hypertension because they have heart failure due to some left heart problems. The other five that really affects women primarily as pulmonary arterial hypertension or pre capillary. This is a problem in the lungs and uh women often wait two or three years before they're diagnosed with this. So echoes are easy to get their fairly cheap and if your if your patients are short of breath and you get an echo in their P a pressure is 60 uh they have a very serious problem and that needs to be worked up and you can I can't overemphasize how much improvement you can see in patients once you treat their pulmonary hypertension. So let's talk about the common one, pre capillary or pulmonary venous hypertension. Um Or This is uh this is pulmonary arterial hypertension, the other 5%. This is due to lung vascular disease. It can be idiopathic due to meth or congenital heart disease. Sleep Apnea, retain pulmonary emboli. As you heard from uh DR KIM stock patients with lupus can have these chronic pulmonary emboli, sickle cell disease. Um, so there's a number of reasons that can cause pulmonary arterial hypertension. This is what this looks like on the echo. Notice that the RV is big, the LV is small, the left atrium is very small. So when I see pulmonary hypertension on the echo, the next thing I look at is how big the left atrium is. If the left atrium small, then they have this pulmonary arterial hypertension. And this is what women have most often. And again, this can be fairly easily treated. Now if you suspect this, you you have to send them for right heart cat, this confirms the diagnosis. Uh otherwise insurance won't pay for the meds. We have to do a vassal dilator trial. We have to rule out a cult congenital heart disease and high output pulmonary hypertension from uh liver disease. But the right heart cath is very safe. It's outpatient. It takes about 15 minutes to do and can be lifesaving for the patient. Maybe you heard recently about the singer Amy Grant who just had heart surgery. She was found to have a rare congenital uh condition, partial anomalous pulmonary venous return for pulmonary vein was connected to her I. V. C. Instead of her left atrium and once you get surgery that's fixed. And this is often missed. This is almost always missed in Children And it's the most common adult congenital heart problem that we see. And I've diagnosed a number of these in our clinic over the years gratifying to diagnose because although you have to do heart surgery it's completely fixable. There's a lot of medications for ph sildenafil to data fill, reassign Gawad at the end of feeling antagonist, process Cyclones and even lung transplant for these patients. Most patients are on two or 3 medications to treat their disease. Um Typically we start to meds like a P. D. Fibers or Viagra type drug plus uh feeling antagonists almost simultaneously. Then we add an oral agents at +123 months. If they continue to have signs of increased risk elevated BMP or reduce six minute walk or high neck veins, we had a third agent. Most often this is an oral agents. Sometimes we use ivy or sub Q. And we send some patients for lung transplant. So pulmonary venous hypertension is the one you see most. This is due to left heart disease. Most of most patients that you see with hef, hef have pulmonary venous hypertension. Any pressure over 40 45-50 is a problem and it means and this is very detrimental to patients over long term. This is what a half path patient looks like with pulmonary venous hypertension. They have a gigantic um left atrium, the left ventricle is normal. Notice how big the right ventricle is. This patient's been sick for so long that the right ventricle has failed. But they always have an enlarged left atrium. There's an easy way to diagnose health path. Uh You use this algorithm called H two path. So have path heavy Body surface area over 30 hypertensive two meds history of hypertension, they get three points for this. If they have Doppler evidence of pulmonary hypertension on the eco age over 60 or special features on Doppler echo E. D. Prime greater than nine. You get points. And even if you just have five points like if you have a fib and you're over 60 And you have hypertension, you have about a 90 risk of having half path in these patients. But if your patients short of breath you get an echo, the efs normal have a big left atrium, especially if they have a fib and their PPA pressure is high, they have half path for sure. So how do we treat this pulmonary venous hypertension? We treat the underlying heart disease, fix the aortic stenosis. We often fix the mitral regurgitation. That's low Ef. Give them the meds I talked about. Diuretics are easy. Diuretics are often under used and patients don't get enough diuretics to normalize their pa pressure. Another thing that we do is we put in the sensor, we can put the small sensor in their pulmonary artery and it tells us what their P. A. Pressures are at home And this reduces hospitalization in both low E. F. and normally have patients by about 30%. And most of our patients who have done this and have hef tough and this really helps them. We're doing a large trial with this device now. Uh and we've finished enrolling randomized 1000 patients. And the question is does this therapy reduced mortality? And we'll know that in the next month or so. So stay tuned. And you may see be seeing a lot more patients with this implantable human dynamic monitor that tells us their P. A pressures if this has been shown to reduce mortality as well. So in conclusion and I think I'm back on schedule. Shortness of breath is a common symptom with many causes after a good history and physical. The echocardiogram really provides important clues about heart failure and pulmonary hypertension. I can't emphasize that enough how useful the echocardiogram is. Unfortunately, many patients, particularly women, have symptoms for years before the diagnosis is made. And the only thing that should have been done was to get an echo earlier, and this is important because therapies exist that can really relieve their symptoms and extend their life expectancy. So let's not delay. I think that's been a theme of this conference. Let's make sure all our patients get a good diagnosis so we can get them on good therapy as soon as possible. Sorry about the glitch in the beginning. Thanks for hanging in there. Thank you very much.