Hello, my name is Sandy McCrary. Today, we're gonna be discussing the guideline-directed medical therapy for heart failure. Much of the information, again, will be derived from the 2022 guidelines for management of heart failure. You have the reference on the screen, and this is an excellent resource for you to have either available electronically or hard copy whenever you're treating heart failure patients. I've also included abbreviations and acronyms that are commonly used in relation to heart failure and will be used during this discussion. And these are just here for your reference. So to begin, I want to just review a small portion of what we discussed during the last module, because the importance of knowing the ejection fraction of the patient that you're treating has significant bearing on the treatment of that patient. The classifications include HFREF, which is a reduced ejection fraction, or an EF that is 40% or less, heart failure with mildly reduced ejection fraction, which consists of an EF between 41 and 49%, and HFPEF, or heart failure with preserved ejection fraction, indicating an EF of 50% or greater. So the guidelines for management of heart failure are issued by the American College of Cardiology, the American Heart Association, the Heart Failure Society of America, as well as the European Society of Cardiology. These guidelines provide us with a very clear direction of drug choice, drug dose, and target dose to be achieved in heart failure patients. Following these guideline-directed medical therapies has been shown to reduce heart failure hospitalization, improve morbidity and mortality, and improve functional capacity for our patients. Guideline-directed medical therapy should be started immediately when that patient is diagnosed with heart failure and are symptomatic. This can be done during the admission process and transition to the outpatient setting. It can also be initiated as an outpatient if that is where the initial diagnosis takes place. Delaying the initiation of these therapies has been associated with never initiating these therapies. And our goal is to achieve optimal guideline-directed medical therapy within three to six months of the initial diagnosis of heart failure for these patients. So in looking at heart failure, we know that heart failure with preserved ejection fraction and heart failure with reduced ejection fraction have both similar as well as exclusive pathophysiologic mechanisms. We'll be looking at that as we go through. They both involve cardiovascular comorbidities and risk factors. There can be systemic disease state, a neurohormonal activation and cardiac injury associated with heart failure with either preserved or reduced ejection fraction. We'll discuss the treatment of HFREF first. And just a reminder, this results from any structural or functional impairment of ejection of blood, causes reduced cardiac contractility and impaired pump function. The mechanism that drive the progression of heart failure is more of a circular process. We have precipitating factors that then lead to cardiac injury. This can then lead to an overactive RAS system and sympathetic nervous system. These systems are initially balanced, but with progression of heart failure, they become imbalanced. We also have natriuretic peptide system resistance leading to that neurohormonal imbalance with LV remodeling, hemodynamic changes, worsening of heart failure symptoms and cardiac injury. So the natriuretic peptide system attempts to counteract the overactivation of the sympathetic and the RAS systems. These over activated systems can bring on not only cardiovascular effects, but also renal and vascular effects. So our job with treating and our goal in treating heart failure is to restore that neurohormonal balance in heart failure. To do that, we have certain medications that address each of these systems. For the sympathetic nervous system, we have beta blockers. For the RAS system, we have ACE inhibitors, ARBs, and now we have ARNIs. And we also have aldosterone antagonist or MRAs. For the natriuretic peptide system, we now have the ARNI. And this is the first drug that we've had to favorably affect the natriuretic peptide system. So the ARNI affects both the natriuretic peptide system as well as the RAS system. So in treating heart failure with reduced ejection fraction, we need to treat and address each of these pathophysiologic mechanisms, the sympathetic nervous system, the RAS system, and the natriuretic peptide system, as well as the novel therapies with SGLT2 inhibitors. So there are four pillars of heart failure treatment with HEP-REF. These include the ARNIs, the beta blockers, the MRAs, and the SGLT2 inhibitors. So looking back in our history of treatment of heart failure, we have some very pivotal trials over the years, going all the way back to 1991 with the SAHLV trial in Alapril, leading up to more current trials in 2022 with the SGLT2 inhibitors. So we're gonna be discussing each of these first-line therapies, beta blockers, aldosterone antagonist or MRAs, the ACE-ARB or ARNI, and the SGLT2 inhibitors. So first we'll be discussing the beta blockers, and these are given in no particular order. These are all considered first-line therapies, but the first one we'll be discussing is the beta blockers. The trials for beta blockers include MERIT-HF for metoprolol-suscinate, Copernicus for carbetolol, and CIBIS-2 for bisoprolol. Beta blockers have been shown to reduce the risk of progression of LV dysfunction and major cardiovascular events. This is not a class effect for beta blockers for HF-REF. There are three beta blockers demonstrated to be effective in reducing the risk of death in heart failure with reduced ejection fraction. The other beta blockers are not included in the recommendation. We should not delay the initiation of beta blocker therapy. Don't wait until symptoms return. Don't wait until their disease progresses in either the inpatient or the outpatient setting. These drugs can safely be started during hospitalization if the patient has clinically stabilized and they're not requiring inotrose. The beta blockers, again, address the sympathetic nervous system activation. They help to reduce sinus rate, and our goal is to reduce the sinus rate optimally between 50 to 60, and that improves outcomes. A greater reduction in resting heart rate has been associated with a decrease in all-cause mortality and hospitalization for heart failure. So I've listed the starting and target doses of the approved beta blockers. Again, there are only three in HF-REF, carbidolol, metoprolosuccinate, and bisoprolol. And one of the first steps that we do when we see a patient that comes to us on HF-REF, if they're on a different beta blocker rather than one of these three, we go ahead and switch them over. The second drug that we'll discuss as a first-line therapy is the aldosterone antagonist, or MRAs. The trials with this include the RAILS trial for spironolactone, Emphasis HF for epleranone. These drugs address the RAS activation in heart failure. They reduce morbidity and mortality. They decrease the rate of heart failure hospitalizations in both HF-REF and HF-PEF, and they reduce the incidence of sudden cardiac death. They are indicated for patients that have an EGFR of 30 or greater, a creatinine of 2.5 or lower in males, 2.0 or lower in females, less than or equal to 5.0, and NYJ class II, III, or IV. Of course, we need to monitor their BMP at baseline, and then again in one week, then again in four weeks, and then every six months after that, after the medication is either initiated or intensified in dosage. The clinical status of your specific patient may require more frequent monitoring or even discontinuation of the drug. Of course, the precautions with the MRAs is the incidence of hyperkalemia and risk of acute renal insufficiency. If the potassium cannot be maintained less than 5.5, then the MRA will need to be discontinued. And I will just say as a side note, the other thing to consider and to look at in your patients that are on MRAs is whether or not that patient is consuming a lot of salt substitute. Some salt substitutes just consist of potassium. The other thing to look at is their dietary intake of potassium. I always give the patient a handout that lists foods that are high in potassium content. And so certainly if we can make minor adjustment, simple adjustment, such as changing their salt substitute or even doing away with it in favor of other seasonings or adjusting their dietary intake in favor of being able to continue the MRA, which has been proven to give significant clinical benefit, then we want to do that. Now, the spironolactone can have antiandrogenic side effects such as gynecomastia or vaginal bleeding. The overall prevalence of this is 10%. So Iplarinol, because it has a higher sensitivity to the aldosterone receptor, is a very effective and good alternative to avoid these side effects from spironolactone. And I've listed, again, just starting and target doses of the MRAs. So next we'll discuss our third first-line therapy in treatment of HEF-REF. This includes the ARNIs, the ACE inhibitors, and the ARBs. And we know that the ARNI is preferred. First, we'll discuss the ACEs and ARBs. These should be considered in HEF-REF if the patient is not able to either tolerate or it is not possible for them to take an ARNI. The trials with the ACE and ARBs include SALV with enalapril, VALHEF with valsartan, CHARM alternative with candesartan. ACEs and ARBs have been shown to reduce morbidity and mortality in patients with an ejection fraction 40% or lower. And this addresses the RAS activation in HEF-REF. As discussed, we know that ARNIs are preferred The trials for ARNIs include Paradigm-HF, which was a very large landmark trial, which looked at Entresto versus enalapril. Again, this was not versus placebo, but versus the previous standard. The trial was stopped early because of benefit versus enalapril. Entresto was associated with reduction in cardiovascular death, Entresto was associated with reduction in cardiovascular death, hospitalization for heart failure, as well as a reduction in sudden cardiac death, regardless of whether the patient had an ICD or not. The Pioneer HF trial looked at the efficacy and safety of inpatient initiation of Entresto in the acutely decompensated heart failure patient. It was shown to have a significantly greater reduction in NT-proBNP levels with Entresto versus enalapril. There was no significant difference in key safety outcomes between the two groups. And this was determined by evidence of any worsening of renal function, hyperkalemia, symptomatic hypotension, or angioedema. So this showed that the Entresto was safe to initiate on an inpatient basis. And it also reduced the risk and composite of death, heart failure readmission, need for LVAD or transplant consideration by 46% compared with enalapril over eight weeks. Finally, the Prove HF trial had primary endpoint of changes in NT-proBNP and cardiac remodeling at one year. This study showed clinically and statistically significant reduction of NT-proBNP levels of 30% from baseline by day 14. And this was maintained throughout 12 months. The signs of reverse cardiac remodeling at one year was both clinically and statistically significant. And there were improvements observed in all parameters of echocardiograms at 12 months. So again, the ARNI is preferred in HF-REF. This is a graph of the landmark trial, Paradigm HF, of Entresto versus enalapril. Entresto showed a 20% reduction in risk of cardiovascular death or first hospitalization of heart failure by 20%. And number needed to treat was 21. And notice that the lines in this study begin separating very early during the trial. So benefit was derived quickly and was sustained throughout the trial. The ARNIs can be safely started during hospitalization. They can be started in a patient who has not previously taken an ACE or an ARB or in a patient who is not yet on a beta blocker or an MRA. They're indicated, again, to reduce the risk of cardiovascular death and hospitalization for heart failure. And they have also been shown to have 35% less decline from baseline in their measurement of health-related quality of life measurements. This was achieved by the Kansas City Cardiomyopathy Questionnaire, which was administered to the patients during the trials. The dosing includes the 24-26, 49-51, and 97-103 milligrams. So it is given BID. It can be up titrated as tolerated, and the target dose is the 97-103. We should monitor a BMP at baseline and in one to two weeks after initiation or any titration of the drug. It is contraindicated, of course, in pregnancy. It does contain an ARB, which is Valsartan, and that is contraindicated in pregnancy, contraindicated with any hypersensitivity to any component of the drug. It's also contraindicated if a patient has a history of angioedema related to previous ACE or ARB therapy. We should also avoid concomitant use of Entresto with any ACE inhibitor. We need to have a 36-hour window in which the patient stops their ACE inhibitor before they start the Entresto. And the reason for that is because if these drugs overlap, there is an increased risk of angioedema. And the same holds true if for any reason they need to switch back from their Entresto to their ACE inhibitor, they still need a 36-hour washout window. And it should also be avoided concomitantly with Alaskarin in diabetic patients. So adverse reactions for Entresto were very comparable to Enalapril. Hypotension, hyperkalemia, cough, dizziness, renal failure, acute renal failure were the most frequently reported adverse reactions, but they were very comparable to Enalapril in the trial. Of course, the most common adverse effect that we see in clinical practice is hypotension. And there are various things that you can do to reduce the likelihood of that occurring and impacting the tolerance of the medication and the ability to up titrate that drug. The patient may be on diuretics. And when they're a uvolemic, we can cut the dosage of the diuretic back or even make it PRN. As we initiate and titrate their guideline-directed therapies, typically their need for diuretics will reduce and they will not have to take as large doses. That has advantage of giving them more blood pressure to then tolerate the guideline-directed therapies. The other thing that I like to do is look at that individual patient's entire medication list. If there is a medication on their list that lowers their blood pressure, but does not have morbidity, mortality benefit for treatment of their HF-REF, then I generally will discontinue that medication. An example of this would be amlodipine. A lot of patients are taking amlodipine to treat their high blood pressure, but it does not have benefit in HF-REF. So in order to initiate and achieve the up titration of their guideline-directed therapies, I will generally discontinue the amlodipine. And that allows the patient to have more blood pressure to tolerate the other medications much better. We do not automatically reduce their diuretic dosage, but that is something else to consider. Because again, as the guideline-directed therapies start to do what they're designed to do, the patient's need for diuretics will likely decrease, and those can be reduced as well. So here is the starting and target doses of ACE inhibitors, ARBs, and ARNIs in HF-REF. But again, remember the ARNI is preferred. It's targeting not only the RAS system, but also the natriuretic peptide system. The ACE and ARBs only target the RAS system. And our final medication in the first-line therapies for HF-REF would be the SGLT2 inhibitors. These drugs have a very interesting history. Prior glucose-lowering drugs were found to engender cardiovascular harm, such as decompensated heart failure and episodes of hospitalizations. So because of this, in 2008, the FDA mandated that any new diabetic medication must demonstrate an absence of cardiovascular harm. So these studies were done as safety trials for diabetes, but the findings were pretty astonishing. There was a dramatic beneficial cardiovascular outcome, not only did they not cause harm, but they brought on significant benefit. This benefit includes a 25% reduction in composite of cardiovascular death or heart failure hospitalization in people with and without diabetes and those with or without prevalent heart failure. The DAPA-HF trial for FORCEGA involved over 4,700 patients and the EMPEROR-REDUCE trial for JARDIENTS involved over 3,700 patients. Was this a statistical quirk? No. Multiple concurrent data sets using all arms of investigation revealed the same conclusion. These drugs reduced de novo onset of heart failure in diabetic patients. So what about non-diabetics? Further studies were done on non-diabetics and this showed that the drug provided benefit not only in diabetics, but also in non-diabetics. So important messages from these trials are that the SGLT2 inhibitors reduce the risk of heart failure hospitalization and cardiovascular death. They improve and prevent worsening of symptoms. They also show a slowing of the deterioration in the kidney function over time. We should consider SGLT2 inhibitors in all diabetics. An important fact is that patients with chronic kidney disease are at far greater risk to die of cardiovascular disease than they are of their kidney disease. The SGLT2 inhibitors reduce the risk of dialysis, transplantation or death due to kidney disease and they also provide protection against acute kidney injury. Albedouria and reduced EGFR are independent markers for cardiovascular death. And importantly, these cardiovascular benefits were obtained on top of the conventional therapies with beta blockers, RNAs and MRAs. So the indication for SGLT2 inhibitors in HEPF-REF, they should be used in conjunction with background guideline directed medical therapies. They are considered first line therapy used in HEPF-REF with or without diabetes in patients that have functional class two, three or four heart failure. They're contraindicated in type one diabetes, pregnancy, lactation, dialysis or patients with a hypersensitivity to the drug or any component. The doses is very simple. No titration is required. 10 milligrams once each morning for Psyche or Jardians. Of course, we need to monitor baseline BMP and then in one to two weeks after the initiation of the drug and then periodically as indicated. The potential adverse reactions include ketoacidosis in diabetics, volume depletion, increased risk for urinary tract infection, genital mycotic infections, hypoglycemia if they are given along with other diabetic medications and insulin. And you may need to consider lowering the dosage of the other agents when co-administering the SGLT2 inhibitor. A very rare, but serious life-threatening condition is necrotizing fasciitis of the perineum or Fournier's gangrene. This is rare, but serious and needs to be dealt with emergently. Initially, when you start an SGLT2 inhibitor, you will expect to see a decrease in EGFR. This occurs because of a decreased pressure in the glomerulus, but that is good in the long run. Generally, there'll be initial decline, but then that stabilizes as the patient continues treatment. Patient counseling when prescribing an SGLT2 inhibitor is very important in the patient's tolerance and ability to continue the medication. We always discuss the two H's when we prescribe an SGLT2 inhibitor. First is the need for hydration. The patient needs to take in at least 48 to 64 ounces of fluid each day. The high urinary glucose loss that occurs with SGLT2 inhibitors causes osmotic diuresis, and that can lead to volume depletion. The risk of volume depletion, of course, is higher in patients who are on loop diuretics. We do not automatically decrease or stop their loop diuretic, but that should be assessed according to your clinical evaluation of that patient. I always recommend to patients that if they cannot eat or drink for any reason, if they are, for instance, if they're told to be in PO for a procedure, or if they have GI symptoms with nausea, vomiting, diarrhea, they should not take the SGLT2 inhibitor while that's going on. Once they are able to eat and drink as they normally would, then they may resume the SGLT2 inhibitor. And again, the reason for this is you want to avoid dehydration in the patient at a time that they cannot be replenishing their fluids by a drug that can cause volume depletion. And you should also consider holding treatment for at least three days before any surgery. And again, the reason for that is because of needing to avoid volume depletion. The second H that we discuss in counseling the patient with an SGLT2 inhibitor is the need for hygiene. We discuss the need to monitor for any signs or symptoms of mycotic infections or urinary tract infections. And there's just no easy way to discuss this other than discussing it. So I've talked to the patient about the risk of these infections, urinary or yeast infections. And a lot of this can be caused because the way the medication works in diabetics is it pulls sugar out through the urine. So if that stays in contact with the skin, there can be a more likelihood of having infection occur. So the way to reduce that risk is by cleaning themselves really well. I tell them clean front and back, wet wipe and dry if needed. And that will reduce the likelihood of the patient having a urinary or yeast infection. Of course, if that does occur, if they do get an infection, then they will either contact their primary care physician or our office. We treat that infection. And I do recommend that while that is being treated, that they stop their SGLT2 inhibitor until the infection is treated, and then they resume taking it. Starting and target doses of SGLT2 inhibitors is very easy. 10 milligrams once every morning. You do need to consider their EGFR. In the trials with Farsiga, the entrance EGFR patient needed to be 25 or greater. And with Jardiance, it was 20 or greater. So just need to watch those levels in determining if your patient is a candidate for an SGLT2 inhibitor. So the mechanisms of action for SGLT2 inhibitors is not completely clear. There are a lot of proposed explanations. We know that inhibiting SGLT2 reduces renal absorption of filtered glucose. It lowers the renal threshold for glucose and thereby increases urinary glucose excretion. This can bring on a reduction in preload, a reduction in afterload, and provides down-regulating of sympathetic activity. This graph is from the DAPA-HF trial showing the outcomes in treating patients with Farsiga versus placebo. There was a 26% relative risk reduction with Farsiga versus placebo in cardiovascular death, hospitalization for heart failure, or urgent heart failure visit. The number needed to treat was 21. Also notice with this trial, lines started separating very early in the trial and sustained throughout. These are results from Emperor Reduced. Jardiance brought on a 25% relative risk reduction in cardiovascular death and hospitalization for heart failure in comparison to placebo. Number needed to treat, 19. And again, notice that these lines began separating very early in the trial and sustained throughout. In addition to the mortality and morbidity benefit, there's also meaningful improvement in quality of life questionnaires with SGLT2 inhibitors. The Kansas City Cardiomyopathy Questionnaire was administered, and there was shown to be a statistically significant benefit in favor of SGLT2 inhibitors in how patients felt. So we'll move on now to other medications to consider in treatment of HF-REF. We'll start with diuretics. They're sort of the mainstay when we're trying to relieve symptoms of heart failure. Symptoms such as dyspnea, swelling fetal legs. The dosage should be titrated to relieve congestion over days to weeks. You may need to reduce the dosage of the diuretic in the setting of increased dosage, doses of their ACE, ARB, or ARNI, or initiation of MRAs or SGLT2 inhibitors. If your patient is requiring a high dose of the loop diuretic, which is equivalent to about 80 milligrams of Lasix-BID, you should consider switching to a different loop diuretic or adding a thiazide diuretic temporarily to the loop diuretic as what we describe to patients as a booster fluid pill. Of course, you must monitor blood pressure, electrolytes, renal function, after initiation and during titration. Another combination of medications to consider would be combination hydralazine plus isosorbide. These can be given as two separate pills together or in a combination pill called Bidyl. The trials include V-Heft and A-Heft. This is a key therapy in certain populations with Hef-Ref, but it's certainly under-prescribed. Hydralazine and isosorbide should be considered in self-identified African-American patients who have NYHA class II, III, or IV Hef-Ref who are on optimal medical therapy. These drugs have been shown to improve symptoms and reduce morbidity and mortality when added to the guideline-directed therapies in African-American patients. Their use in non-African-American patients apply to patients who remain symptomatic even though they're on maximally tolerated doses of therapy. They are also very useful in patients who have current or previous symptomatic Hef-Ref, but they cannot be given first-line agents because of either drug intolerance or renal insufficiency. This is a very good option for those patients. Other medications to consider, and we'll just cover these briefly, Digoxin, it really lacks any new data. Most of its use in modern heart failure with reduced ejection fraction focuses on its role as a rate control agent for atrial fibrillation in patients who have low blood pressure. It may be considered with symptomatic Hef-Ref despite guideline-directed medical therapies to decrease hospitalization for heart failure. It did not improve cardiovascular or all-cause mortality. Avabradine or Corlanor from the SHIP trial may be used in patients who have stable, symptomatic chronic heart failure, Class II or III, with an ejection fraction 35% or lower, who are in sinus rhythm and continue to have a heart rate of 70 or greater, even though they may be on maximum tolerated doses of a beta blocker, or they may have a contraindication to a beta blocker. By adding this drug in this setting, you can reduce risk of hospitalization for heart failure. And finally, Vercuvo in the Victoria study, this drug may be used in patients with Hef-Ref who have worsening heart failure symptoms and are already on guideline-directed medical therapies. This can be added or considered to be added to reduce the risk of cardiovascular death, hospitalization for heart failure, following an admission for heart failure, or a need for outpatient IV drug therapy with diuretics in patients who have an EF 45% or lower. So we'll spend a moment talking about the up titration of these drugs. Generally, low starting doses of beta blocker, ACE, ARB, or ARNI are better tolerated in patients. Of course, the plan is to up titrate each of these drugs because we want to reduce their CV mortality and hospitalization for heart failure. We titrate and optimize guideline-directed therapies as frequently as every one to two weeks. So even though you start that dosage low, it will not stay low if possible. It will be titrated to hopefully to target dose. But of course that will depend on the patient's symptoms, vitals, and lab studies. You should monitor for any changes in heart rate, blood pressure, electrolytes, renal function, or any symptoms with any dosage change. You may need to delay a planned up titration of a heart failure medication until any adverse effects they've observed from the lower dose resolves. If the initial attempt fails, then don't be afraid to re-challenge with that higher dose at a later date. Repeated attempts after reassessment can be very successful. About 70 to 80% of patients enrolled in clinical trials were able to tolerate short, intermediate, and long-term treatment with these agents and were able to achieve and maintain target doses. We will also look at the sequencing of these drugs. All four drug types need to be initiated and up titrated. But what order is best? Well, that really depends on your patient. That should be individualized according to their symptoms, their vital signs, their tolerance of medications, what their functional status is, their renal function, electrolytes, any comorbidities, the specific cause of heart failure. For instance, if your patient has a tachycardia induced cardiomyopathy because of AFib with RBR that they developed, then initiating the treatment with the beta blocker may be more helpful in that patient because you're wanting to control that heart rate. The use of all four drug classes has been estimated to reduce all-cause mortality by 73% compared with no treatment. So that is the importance of these medications, and getting all four of these on board and titrated to target doses. Next, we'll discuss the treatment of HEF-PEF. Again, this results from any structural or functional impairment of ventricular filling of blood causing impaired ventricular relaxation, abnormal LV filling, elevated filling pressures, and an impaired response to stress. The treatment goals with HEF-PEF include four things. Number one, diuretics to manage their volume status. Number two, SGLT2 inhibitors. These have been shown beneficial in decreasing hospitalizations for heart failure and CV mortality. Number three, we need to attain blood pressure targets for these patients. This helps to prevent morbidity. This can be achieved with MRAs, ARBs, or ARNIs, and is beneficial in decreasing hospitalizations, especially if the EF is toward the lower end. And also, we need to manage any atrial fibrillation if the patient has that to improve their symptoms. SGLT2 inhibitors are also indicated in heart failure with mildly reduced ejection fraction and HEF-PEF. With Jardians, the improved preserved study demonstrated improved heart failure outcomes among patients with HEF-PEF and heart failure with mildly reduced ejection fraction versus placebo. And the benefit in this study was primarily driven by a reduction in hospitalizations for heart failure rather than mortality. With Farsiga, the preserved AGF trial demonstrated significant improvement in symptoms versus placebo. This included improved symptoms of physical limitations, six-minute walk tests, and this benefit was seen at 12 weeks. The Lidliver trial demonstrated improved clinical outcomes in patients with heart failure with mildly reduced EF and HEF-PEF versus placebo. And this is just a graph of the Emperor preserved trial showing the relative risk reduction, composite CV death and heart failure hospitalization for Jardians versus placebo. Again, these lines started separating very early in the trial, statistically significant from day 18. I've just put this for reference for you. This is just a list of medications that should be avoided if possible in heart failure because they can exacerbate or worsen symptoms or renal function. And these are just medications to look over when you're considering the other drugs that your patient may be required to take. Finally, we'll discuss device therapy in HEF-REF. ICDs are indicated for primary prevention of sudden cardiac death to reduce total mortality. The patient though needs to have a reasonable expectation of survival of one year or greater depending on their other comorbidities. They should be considered if the ejection fraction remains 35% or lower with class two or three in a patient who is on guideline-directed medical therapies and also in patients post-MI if they are on guideline-directed medical therapies. The patients with genetic arrhythmogenic cardiomyopathies with high risk features of sudden cardiac death and an EF of 45% or lower should be considered for an ICD. And again, it is not indicated if the patient has comorbidities or frailties that would limit their survival with good functional capacity to less than a year. CRT is also beneficial in reducing total mortality as well as reducing hospitalizations and improving symptoms and quality of life for HEF-REF patients. This should be considered when there is a left bundle branch block present if the ejection fraction is 35% or lower in YAJ class two, three, or ambulatory four and the patient is on guideline-directed medical therapy. I've put here the QRS duration information which you can refer to that. So in these patients, the consideration of a biventricular ICD is very important. It is not, however, indicated if they have comorbidities or frailty that would limit their survival to less than one year. And the other group of patients to consider this in would be those who are on guideline-directed therapy. EF remains 35% or lower. They already have perhaps a pacemaker or a single chamber ICD. And maybe you wanna anticipate them needing upgrade to a biventricular ICD. Upgrade to a biventricular ICD. But it's not indicated, again, if there are comorbidities and frailty limit the potential survival with good functional capacity to less than one year. There are some specific populations to consider when treating heart failure. First, we'll discuss African-American patients. So many clinical trial populations, including those for ARNIs, SGLT2 inhibitors, and ivabradine had few or no African-Americans represented in the trials. But because of the established benefits that we've seen in the general population, heart failure guideline-directed therapies are still recommended for African-American patients, including the use of beta blockers, ARNIs, MRAs, SGLT2 inhibitors. And of course, in this population, we also should consider the addition of hydrolyzine-isosorbide combination. The survival benefit with the combination, hydrolyzine and isosorbide, is isolated to those patients of self-defined African-American race. Both ARNI and hydrolyzine-isosorbide should be considered. It's not an either-or. The hydrolyzine-isosorbide is added to guideline-directed therapies. And we know that the risk of angioedema with both ACE inhibitors and ARNIs is higher in the African-American patients. So that is certainly something to consider. Another population with special consideration would be older Americans. The upper range for inclusion in most heart failure clinical trials was typically 75 plus or minus five years. Nevertheless, we should still target the doses for guideline-directed therapies in older patients, but we will need to closely surveil them for any adverse drug reactions. So all the treatment, hopefully we will see some recovery in LV ejection fraction in HFREF. Outcomes improve when there is recovery to greater than 40% in the setting of an ejection fraction that had previously been less than 40%. But what about patients who have complete recovery of their ejection fraction? Should we continue guideline-directed therapies or should we reduce or eliminate it in these patients? Well, this was looked at in a trial called the TREAD-HF study. And this was a study looking at the withdrawal of pharmacologic treatment for heart failure in patients with recovered dilated cardiomyopathy. And they found that nearly 50% of subjects that were withdrawn from their guideline-directed medical therapies had a heart failure event in six months. So in the absence of a defined reversible cause for their HFREF, such as tachycardia-mediated cardiomyopathy, then the current guideline-directed medical therapies should be continued in this patient. This is a slide for your reference. This is also in the guidelines. It's just a very good overview looking at the stages of heart failure as well as risk factors for each type of patient and the therapies for each. So in summary, we feel like with heart failure so many times we're just putting out fires. Patient's symptomatic, they're decompensated, and we're having to address that decompensation. I want to challenge you that while putting out these fires is very important and very helpful from a symptomatic standpoint in heart failure, we as providers need to move beyond just treating their heart failure symptoms. We need to get all heart failure patients on guideline-directed medical therapies that address the underlying disease process and also offer morbidity and mortality benefit. Starting guideline-directed medical therapy immediately upon diagnosis of heart failure in the symptomatic patient should be done in the inpatient setting during admission and transition to outpatient setting or initiated in the outpatient setting if that's where it is initially diagnosed. Our treatment needs to include therapies that address all of the pathophysiologic mechanisms, including the sympathetic nervous system, the RAS system, the natriuretic peptide system, and the SGLT2 inhibitors. If we delay initiation of these guideline-directed therapies, then that is associated with never initiating these guideline-directed therapies. The use of all four drug classes has been estimated to reduce all-cause mortality by 73% when compared to no treatment. So certainly we need to move beyond symptomatic treatment to treating the underlying causes because our patients really deserve that treatment. I have some references here that we used throughout this presentation. And that concludes the guideline-directed medical therapy module for heart failure. Next, we'll be discussing some case studies and working through the process of assessment and treating those patients. So hope to see you there. Thank you.

heart failure

ejection fraction

guideline-directed medical therapy

medications

dosing

monitoring

device therapy

comprehensive treatment