Speaker 1:This program is presented by Medscape Education Global.

Dr Zieroth:Hello, I'm Shelley Zieroth, Professor Rady College of Medicine at the University of Manitoba, and director of heart failure and heart transplant clinics in Winnipeg, Canada. Today, I'd like to review some of the key points that were discussed in a program titled, Taking Action in Heart Failure: The Universal Language of Success. [00:00:30] In this program, we used a patient case, Christina, to discuss the recognition and diagnosis of heart failure with reduced ejection fraction, and the treatment of patients with HFrEF and other cardiovascular comorbidities, such as dyslipidemia, and using guideline directed medical therapy to do so.

Let me start with the case presentation of Christina. She's a 63 year-old woman, who presents to the emergency department [00:01:00] with congestive symptoms, meaning shortness of breath, leg edema, and a five kilogram weight gain. She hasn't had any recent chest pain. And last summer, she was able to walk about 1.5 miles, and she's had a significant decline in her exercise tolerance. Now, some information that's going to be important in deciding what treatments to initiate includes her vital signs. Her blood pressure is 145 on 92. Her [00:01:30] heart rate is 68. And she has an elevated respiratory rate of 24, and she's afebrile.

When you ask about her medical history, well, she, in fact, had a heart attack at age 52. She also has some cardiac risk factors, including hypertension, hyperlipidemia for 15 years, and an eight year history of type two diabetes. And some other common comorbidities occur in this patient as well, including depression [00:02:00] and obesity. Now, in terms of her medications, she's already on quite a few, and we'll have to look at these when we decide what therapies we're going to start her on in hospital. She's on a puffer. She's on aspirin. She's on canagliflozin an SGLT2 inhibitor. She's on candesartan, an ARRB, Metformin, metoprolol, a beta blocker, sertraline and simvastatin. So you see, because of her comorbidities, she already [00:02:30] has some elements of the four foundational therapies, but we can do better.

Now, when you examine her, she shows signs of volume overload, including an elevated JVP. She has an S3 and S4 and a fairly loud mitral regurgitation murmur that registers as a three out of six. She has crackles to her lower lung fields, and she does have peripheral edema as well. [00:03:00] Lab work comes back and she has chronic kidney disease, with an EGFR of less than 60. She's not anemic at this time. Her hemoglobin A1C is 7.2% and her NT-proBNP, a marker of heart failure, a biomarker that we use to diagnose heart failure, is really quite elevated at 4500 picograms per deciliter.

Now, her x-ray [00:03:30] confirms pulmonary edema and cardiomegaly. And her EKG shows a fairly common pattern that we see in patients with a cardiomyopathy, which is a left bundle branch block. In the emergency department, she's started on spironolactone, and she's on IV furosemide, as well. She gets diuresed about a liter and a half, which is good, she's having an improvement in her symptoms, but there's still room [00:04:00] to go. And cardiology is consulted, "Well, what can we do to improve her heart failure therapies and her overall outcome?"

First of all, we talked about the diagnosis of heart failure. And the natriuretic peptide was really a very important element of biomarker, which can diagnose heart failure in patients presenting with shortness of breath and dyspnea. And another important test to order and to confirm the diagnosis [00:04:30] of heart failure is an echocardiogram. And in Christina's case, her echocardiogram demonstrated an injection fraction of under 40%. In fact, it was 33%, and this confirms a diagnosis of HFrEF. How would you approach her treatment here?

Now, I think that there's two different things to think about here. There is the addressing the residual risk with regards [00:05:00] to her heart failure, but also addressing her residual risk related to her other cardiac risk factors. We're also going to take the opportunity, during this hospitalization, to provide her with education, and we're going to optimize her guideline directed medical therapy for HFrEF. When we do that, we're essentially going to improve her survival, and we're going to reduce her risk of hospitalization [00:05:30] related to heart failure. And in fact, the four foundational therapies also result in an improvement in functional status.

I mentioned reducing the residual risk related to her cardiac risk factors, as well. And in fact, there are often many comorbid conditions in patients with a diagnosis of heart failure, and that can include diabetes, hypertension, hyperlipidemia, chronic kidney disease, like she has, sleep disordered [00:06:00] breathing and frailty, and these all have to be considered. But let's focus on dyslipidemia. That's actually something that I don't often focus on as a heart failure cardiologist, and there is a layer of residual risk there as well in reducing future adverse cardiac events that we should address.

And in the discussion in the symposium, we proposed that we would switch her simvastatin to a more potent statin, such as [00:06:30] atorvastatin or rosuvastatin, and also potentially consider ezetimibe, and, if necessary, PCSK9 inhibitors in order to get that LDL down as much as possible and to reduce her risk. So pay attention to that lipid profile, even heart failure cardiologists, if you haven't been looking at it, please take the whole patient into consideration to minimize residual risk. There's also [00:07:00] the potential of diabetes risk, as well, we talked about. We can reduce her residual risk. She's on an SGLT2 inhibitor. There are other drugs that improve cardiac events and reduce hemoglobin A1C, as well as weight, including GLP1 receptor agonists, which might need to be considered in Christina's case, as well.

But let's pivot and focus on this admission for heart failure and a new confirmed diagnosis of HFrEF. [00:07:30] In fact, she's at risk of another hospitalization in the future. And although she's on what may be the traditional four foundational therapies now with candesartan, a beta blocker, an MRA and an SGLT2 inhibitor, we had a discussion about what would be most beneficial in terms of reducing her residual risk. And we reflected on the series of international guidelines that prioritize [00:08:00] those four foundational therapies with RASI therapy, with ARNI being the preferred agent, beta blocker, MRA and SGLT2 inhibitors. And that is present in the 2021 Canadian Cardiovascular Society Guidelines. That is reflected in the very recent ESC HFA Guidelines, as well. As well as in the 2022 AHA ACC HFSA Heart Failure Guidelines.

[00:08:30] You apply those four foundational therapies, even at low doses, and you can do that in hospital, as well. They become the four pillars of HFrEF therapy. Many of these guidelines also discuss the urgency to get all four drugs on board, but still to achieve the target doses. Some even speak about four drugs in four weeks. A lot of this is done as an outpatient in the chronic ambulatory [00:09:00] heart failure clinics. However, there are opportunities to prescribe guideline directed medical therapy, as well as an inpatient. And we have data with regards to initiation of sacubitril-valsartan in hospital, in the PIONEER-HF trial.

And in this trial, patients were randomized to enalapril versus sacubitril-valsartan in hospital. And what we saw was there was a significantly reduced [00:09:30] levels of NT-proBNP at followup at eight and 12 weeks. And on further post hoc endpoints, we saw reductions in the risk of need for transplant, mechanical circulatory support and re-hospitalization. So this really is going to be beneficial to start Christina on in hospital. And because she was on an ARB, we can easily switch to sacubitril-valsartan. If the patient was on an ACE inhibitor, we [00:10:00] would require a 36-hour washout before initiating sacubitril-valsartan in hospital.

And we spoke about a helpful hint. Some people, if a patient is on an ACE inhibitor on entering the hospital, they immediately switched them to an ARB to avoid a delay sacubitril-valsartan initiation in hospital. And we also know, from PIONEER-HF, that in hospital initiation of sacubitril-valsartan is, in fact, safe. Now, she's already [00:10:30] on an SGLT2 inhibitor, canagliflozin, and one could hypothesize with the recent EMPULSE trial data that we could switch her SGLT2 inhibitor to empagliflozin, because of the outcome in that trial. There's less in hospital initiation data with regards to canagliflozin, but in order to simplify her medication regimen, we discuss, potentially, we would just leave her on canagliflozin for now, with the priority being for switching [00:11:00] the candesartan to sacubitril-valsartan in hospital.

Now, in addition to adjusting her medications and getting her on optimal therapies, we would also refer her to cardiac rehabilitation. This can be an often neglected and forgotten important step in the education and recovery of patients following a heart failure hospitalization.

Now, after hospitalization, [00:11:30] when you're following her in clinic, this is going to be your opportunity to up titrate those medications further. And there are actually guideline recommendations to see patients within seven to 14 days of hospital discharge in order to do just that, and further address the residual risk by up titrating these four foundational therapies. So when it comes to up titrating her medications, depending [00:12:00] on her blood pressure, we would up titrate her sacubitril-valsartan. Depending on her heart rate and blood pressure, we would up titrate her beta blocker. And of course, for any RASI therapy up titration, we'd be keeping an eye on her EGFR and her potassium levels. We're going to try to get to target doses as soon as we can. Typically, within three months, sometimes it takes six months, if the patient lives far away from your clinic, but why [00:12:30] are we doing that?

Because we have favorable data from trials, like the PROVE trial, for instance, in which patients who were switched to sacubitril-valsartan, and up titrated over time, at one year followup, they had an almost 12% increase in their ejection fraction. Why is this important? Because if you give them the opportunity to remodel by optimizing those four foundational therapies, we might avoid [00:13:00] need for referral for an ICD with such dramatic improvements in ejection fraction over time. Now, it's important to recognize that there's shared decision making when it comes to medications and initiating medications for heart failure therapy, but it really is important to discuss with patients their benefits, in terms of a reduction in death, cardiovascular death, reduction [00:13:30] in heart failure hospitalization, and improvement in functional status, as well.

There's often quite a bit of pill burden in our patients with heart failure. And there's often, sometimes, a request as to whether or not they can come off these medications. And I would allude to the TRED-HF trial, which demonstrated worsening outcomes in patients who had withdrawal of drug therapy. And so, it's important to continue these medications, even [00:14:00] if they've had an improvement in their ejection fraction over time, which we, in fact, anticipate with the initiation of these four foundational therapies.

So to recap what we did with Christina when she presented to hospital. We got an NT-proBNP, which raised the suspicion and confirmed a diagnosis of heart failure. We got an echocardiogram, which also confirmed a diagnosis of HFrEF. We knew that her ejection [00:14:30] fraction was 33%. We de-congested her, and we looked at ways to optimize her guideline directive medical therapy. And our most important step there was switching her candesartan to sacubitril-valsartan. We then followed her up rapidly in outpatient clinic, where we then addressed getting to the target doses of these medications, as well. That will provide an opportunity for the heart to remodel [00:15:00] and potentially, with an improved injection fraction, we can avoid the need for device referral.

So this is great news for Christina, and it may mean we move from heart failure to heart success with the use of our four foundational therapies in this case. Thank you for participating [00:15:30] in this activity, and please continue on to answer the questions that follow and complete the evaluation.

Speaker 1:This program was presented by Medscape Education Global.