Hi, my name is Michelle Weber. I'm a board certified nurse and acute care nurse practitioner. I have my master's of science degree in acute care from the Wright State University in Dayton, Ohio. I've been a nurse for over 24 years and a nurse practitioner for the last 16. I've obtained my DMP, or doctor of nursing practice, at the University of Alabama in Huntsville in May of 2020. I will be talking about sudden cardiac death prevention and advanced therapies. I will be discussing generic and trade name medications, and these will be listed for guideline direct and medical therapy for heart failure. There will be some commercial names listed, but these will be related to where you can find heart failure technology. Some of my objectives are to overall define what heart failure is, to talk about the epidemiology of heart failure, to list the four pillars of heart failure and treatment, summarize when an ICD should be used, and to compare the indications and exclusion criteria for advanced therapies such as mechanical support and heart transplant. I'll start off with a little heart failure facts. Heart failure is worldwide and it is on the rise affecting more than 20 million individuals. It is estimated that incidence increases as individuals get older from 6 to 10 percent over the age of 65. According to the CDC, the prognosis of heart failure is poor, noting that after diagnosis the survival rate is only 50 percent. The annual cost related to heart failure is estimated at 30.7 billion dollars related to medications, health care services, as well as miss work. Heart failure is defined as a clinical complex syndrome that assigns and symptoms of structural or functional cardiac dysfunction that can be the result of ventricular inability to fill or eject blood. Unfortunately, due to the symptoms of heart failure, there's increased hospitalization, increased morbidity, and increased complex regime. The symptoms can be that of systolic or diastolic, which we'll discuss a little further in the follow-up slides. So we'll define heart failure a little more. Heart failure classification is determined by the individual's ejection fraction. If the ejection fraction is less than 40 percent, it is called heart failure with reduced EF. Heart failure with ejection fraction greater than 50 percent is that of heart failure with reserved EF. You'll also note on the slide we have heart failure with a mid-range of that 40 to 49, as well as that heart failure improved EF, which is greater than 40, and this is our goal. For individuals with heart failure, we also look at classifications as well as staging. Just because an individual has a diagnosis of heart failure, what does that mean to them? As you can see, if there's a structural change, it'll be that in the staging. Going on to more of the symptoms will be the functional class. Given their symptoms, they are strategized by the degree of heart remodeling in symptoms. Heart failure classification is divided in stages, which the individual moves from A down to D, but they cannot move up unless they receive a heart transplant. The functional classification can change depending upon how an individual's systems are at that given time. The pathology of heart failure starts when there's change in the heart muscle for a variety of reasons, from coronary disease to inflammation. From coronary disease to infiltrative disease. The body attempts to sustain cardiac output and arterial blood flow through our activation of the neurohormonal systems of the renin angiotensin system. That causes vasoconstriction and sodium and water retention. This causes ventricular remodeling and myocardial hypertrophy. This change or modeling makes the heart go from a football shape to that of a basketball shape. This illustration also shows the difference between diastolic and systolic heart failure. In diastolic heart failure, the ejection fraction is likely normal, so the heart squeezes okay, but is unable to relax. Over time, the ventricle becomes stiff and thickened. In systolic heart failure, the ejection fraction is usually low, the ventricle becomes enlarged, and the heart wall thins. To help individuals with heart failure, we have guidelines that help to prevent and reverse that of the heart muscle damage and also decrease hospital admissions and mortality. One of the first step is to get individuals on what we call goal-directed medical therapy, and through education and close follow-up, we titrate and monitor these medications. The first class of medications to start with in heart failure is that of an ARNI, which is angiotensin receptor nebulizing inhibitor. This diagram shows the algorithm of heart failure and the medications that are used. The four major medications are noted in heart failure are the four pillars of heart failure guidelines. The goal is to initiate and optimize the four pillars of medication. All the agents are initiated in parallel. There is follow-up and close titration so that the medications are titrated up over time. Additional therapies can be considered as the patient progresses through their heart failure. Of the medications, we have ARNIs, beta blockers, the mineral corticore receptors, and that of the SGL2 inhibitors, which we will discuss more. Going back to our discussion of what an ARNI is, an ARNI is a combination of two medications, which is Secubitrol and Valsartan. It is initiated at low doses of 24-26 for twice a day and titrated up. Blood pressure monitoring, as well as renal and potassium function are needed. The initiation of ARNIs, ACEs, and ARBs are better tolerated when a person is wet, and beta blockers are more tolerated when an individual is dry. The Paradigm trial was a trial that was used for evaluation of ARNIs. Initially, ACEs were used, and they were the cornerstone for treatment for heart failure, and these studies were originally 25 years ago, looking at enalapril and the reduction of death. The Paradigm trial used that of a double-blind trial of 8,442 individuals, looked at the use of ARNIs versus enalapril. The primary outcome was looking at death and hospital re-emissions. The trial was stopped early, after 27 months, due to ARNIs having superior effects over that of enalapril to reduce the risk of death and hospitalizations and heart failure. To talk a little bit about how ARNI works, as mentioned, ARNI is a combination of two medications. Secubitrol is a pro-drug that promotes vasodilatation and reduction of the volume via the sodium excretion, causing eventually reduction in preload, as well as ventricular remodeling. Valsartan is that of a medication that inhibits the angiotensin II, causing reduction in vasoconstriction, sodium retention, and as well, reduction in myocardial hypertrophy. Monitoring for an ARNI is much like that of an ACE or ARB. Renal function potassium are needed to be monitored about 7 to 14 days after initiation of therapy. This also includes any titration of therapy. This table reviews the major adverse effects and dose titration forms. If a patient is on ACE, just remember there's a 36-hour washout period before an ARNI can be started. So let's talk a little bit about ACEs. If a patient is unable to tolerate an ARNI, you can work on titrating up an ACE. ACE medications end in prils. Please note that here we have captopril and nalopril, licenapril, and verapamil. Here's the initial doses, and it's in the goal for the target doses. Solved was the trial that was used to study nalopril. Solved was a double-blind placebo-controlled study of 2,569 individuals, dating back to 1986 to 1989. The overall outcomes of the use of nalopril showed that there was a 16% reduction in mortality. ACEs have a similar monitoring to that of ARBs or ARNI. The major side effect is angioedema that needs to be watched for and can happen at any time, not just on initiation of the medication. The most common side effect is a dry cough and can be resolved by switching the patient to a medication of an ARB versus an ARNI. As well as watching the renal function, looking at major side effects, an ACE should be titrated every one to two weeks while monitoring that of the renal function, the potassium. If there is any side effects, depending upon the side effects, if there's hypotension, the dose can be decreased as well. Let's talk a little bit about ARBs. ARBs are angiotensin receptor blockers, and these are the sartans. As you see on this slide, losartan, valsartan, and candesartan. The doses are also listed as well as the starting doses and the goal titration dose. Once again, the monitoring for an ARB is going to be that of renal function of potassium as well as vital signs. Major adverse effects include that of dizziness, hypotension, rash, and once again, angioedema and cough. The dosage should be titrated starting at low doses and titrating up. I've included this diagram to show the way that ARBs work by blocking the angiotensin II that causes blood vessels to constrict. The ARB helps to expand the blood vessels to lower the blood pressure and make it easier for their heart to pump. The next class of medications we'll talk about is adastrone antagonists, which are that of a plurinone and spirolactone. The reason this class of medication is approved is because adastrone is a steroid hormone that increases sodium retention and that of magnesium and potassium loss. Adastrone may ultimately also cause myocardial fibrosis, vascular injury, and direct vascular damage leading to and development of heart failure. The use of adastrone antagonist has been shown to slow the heart failure progression and prevent that of the heart failure remodeling and also reversing. The RAIL study looked at 1,663 patients with that of heart failure and randomized them getting spirolactone as compared to placebo. The addition of spirolactone as well as other gold rectum medical therapy was found to both reduce mortality and death among patients with heart failure. For adastrone antagonists, it is very important to monitor renal function as well as potassium. The major side effect with spirolactone is gynemastia that occurs in about 25 percent. If gynemastia does occur, please educate your patient that it may occur, but if it does occur, make sure that you switch them to a plarinum. The next class of medications that we'll talk about is beta blockers. We'll mostly be talking about curbetalol and metoprolol succinate. The Merit Heart Failure Trial was a double-blind placebo-controlled randomized trial of 3,991 patients. These individuals had class 2 to 4 heart failure and ejection fractions less than 40 percent. The primary endpoint for this study was looking at morbidity. This study was actually stopped early because they found that individuals on metoprolol actually had a reduction of mortality with that of 7 percent compared to 11 percent. Now we'll talk a little bit about the Copernicus Trial. The Copernicus Trial looked at the use of curbetalol. It was a trial of 2,289 individuals over 152 sites, and the individuals were randomized to either curbetalol or placebo for a mean of 316 days. The study was also stopped short due to a high significant mortality benefit with curbetalol of 35 percent. Beta blockers have been shown to reduce remodeling in heart failure, increase ejection fractions, as well as reduce the end systolic volume and improve ventricular filling. The monitoring of beta blockers is noted on this slide. The goal is to look at the heart rate as well as blood pressure and monitor individuals for dizziness or lightheadedness. The last pillar is that of SGL-2 inhibitors or sodium glucose cotransport-2 inhibitors. These two medications have heart failure indications for that of heart failure reduced EF as well as heart failure preserved EF with and without diabetes. These are for individuals with New York Heart Association class 2 through 4. SGL-2 inhibitors function through a novel mechanism of reducing the renal tubular glucose reabsorption, producing a reduction in blood glucose without stimulating insulin release. Other benefits may be that of better blood pressure as well as weight. The DAPA heart failure trial is a phase 3 placebo-controlled trial that had to randomize 4,744 individuals with that of New York class 2, 3, and 4 heart failure with ejection fraction less than 40 percent. The primary outcome was that of looking at heart failure, hospitalizations, and cardiac death. This slide shows that there was a reduction in overall cardiovascular deaths and hospitalizations in that of patients with heart failure with and without diabetes by over 20 percent. In this slide, you also note the all-cause mortality data reduction of cardiovascular deaths of 18 percent and hospitalizations of 30 percent in patients with heart failure. In SGL-2s, hypotension and hypovolema need to be watched for. Individuals with renal impairment who are elderly as well as on a loop diuretic are at increased risk for volume depletion and hypotension. Consider decreasing diuretics when starting these medications. Ketoacidosis in patients with diabetes as well as infections such as necrotizing fasciitis needs to also be watched for. If an individual is PO, NPO, nothing by mouth, they need to be educated that they need to hold their SGL-2 inhibitor. I'd like to talk a little bit about vasodilators that are used in heart failure. The first medication is hydralazine. The hydralazine is a three times a day medication, so education needs to be done to make sure the individual can get in all three doses. The other two class of medications of that is Iserdil and a combination of hydralazine and Iserdil. It is note that isosorbide mononitrate is not recommended by the current guidelines. All these medications are three times a day medications, so education is needed to be done with your patients. With vasodilators, blood pressure as well as shortness of breath will need to be monitoring. The major side effect for most individuals is that of headaches, dizziness, or lightheadedness. There is also lupus type syndromes that can be seen with hydralazine. The medications as well as education needs to be done that nitrate should be six hours apart and the dosage should be started low and titrated up from there. Tylenol can be given if individuals do have a headache. Another medication to consider for your heart failure patient is Vabradine or Colurnor. Vabradine is indicated for individuals that have ejection fraction less than 35 percent, that they are on maximum dose of beta blocker, but they still have a resting heart rate greater than 70% and are class two to three of heart failure. The SHIFT trial was used to look at avabridine. It was a randomized 6,558 patients that had heart failure with class two to four, ejection fraction less than 35% and recent hospitalizations within the last year and heart rate greater than 70. In this study, avabridine versus placebo was used to look at overall improvement of that of hospitalizations and mortality. At the medium followup of nearly two years, avabridine therapy was associated with 5% absolute reduction as the primary endpoint driven by both a 5% absolute reduction in hospitalizations for heart failure and 2% of that of heart failure mortality. A monitoring for avabridine is that of mostly of heart rate and cardiac arrhythmias. Individuals should be monitored for bradycardia as well as atrial fibrillation. Two of the common inotropes that are used for heart failure with myocardial contractility dysfunction is that of diputamine and milrinone. These inotropes help to improve the perfusion, decrease congestion, and also augment diuresis and that of renal and other organ perfusion. Although long-term inotrope therapy has been shown to increase mortality, inotropes can be used to bridge an individual to advanced therapies such as a left ventricular assist device or transplant. In situations where a patient is not advanced therapy candidate, then inotropes can be used for palliation to help with symptoms relief at end of life. The two medications as mentioned are diputamine and milrinone. You can see the doses there as well as the receptors that they assist. I would like to talk a little bit about ICDs. The placement of ICD should be considered if an individual has had a reduction in their LVEF or ejection fraction that's less than 35% despite three months of optimal pharmacological therapy. CRT or cardiac resynchronization therapy should be considered if the individual is in sinus rhythm, has an ejection fraction that still remains below 35%, a left bundle branch block, a QRS that is greater than 150 milliseconds, as well as a New York Heart Association class two, three, or four symptoms in his own optimal therapy. This diagram shows that of heart failure management, noting that we've already discussed guideline-directed medical therapy. If an individual is in acute decompensated heart failure, start with vasodilators and diuresis. Consider inotrope therapy as well as mechanical circulatory support and cardiogenic shock. So what happens if an individual with systolic heart failure continues to decline? There should be consideration for mechanical support with a left ventricular cyst device as well as that of heart transplant. This slide notes a potential algorithm for that of a patient with stage D systolic heart failure and looking at the candidacy versus that of mechanical support or an LVAD versus heart transplant. It is noted in the United States, there are 3,990 individuals that are currently waiting on a heart transplant list. Despite many campaigns to increase donor volume by local and federal agencies, the donor supply has remained flat and is limited to only approximately 2,500 heart transplants annually in the United States. Another thing to consider is the severity of illness. We look at the Intermax. The Intermax is a North American registry established in 2005 that collects clinical data for patients receiving mechanical circulatory support device therapy to treat advanced heart failure. The Intermax scale assigns patients with advanced heart failure into seven levels according to their hemodynamic profile and functional capacity. In this slide, we'll know the FDA approval status for that of ventricular cyst devices or mechanical circulatory support systems and where they're approved as well as the New York Heart Class Association. All right, now we're gonna move on to a different topic of that of left ventricular cyst devices. The indications for an LVAD placement of that of short-term for myocardial recovery, long-term as far as bridge to transplant or BTT, and also long-term for destination therapy for individuals who are not transplant candidates. Indications for an LVAD are class four, stage D heart failure with ejection fraction less than 25%. These individuals are usually in refractory cardiogenic shock with the Intermax category of one. Individuals may be dependent on a balloon pump or other temporary mechanical support devices such as an Impeller or ECMO for greater than seven days. Individuals can also be considered for mechanical support if they're on continuous inotrope therapy with Intermax category two or three for greater than 14 days. There needs to be evidence of poor cardiac output by that of the right heart cath measuring the cardiac output, cardiac index, as well as hypotension. Individuals are monitored by a cardiopulmonary exercise test and usually have a VO score of less than 14%. Now we will talk about long-term circulatory support devices of different types of LVADs. The original FDA approved LVAD was the HeartMate XVE for destination therapy in 2002. However, despite the early first generation pumps, it was not widely used and there was only about 119 DT implants in 2003 as compared to 377 in 2005. Physicians and patients were concerned regarding the large pump size, adverse effects, limited durability, as well as the short-term use of the device for 18 to 30 months. The HeartMate XVE production was discontinued. Contemporary, secondary, and third generation LVADs are valveless pumps that utilize a permanent magnetic field designed to rapidly spin a single impeller supported by mechanical and or more recent hydrodynamic or magnetic bearings. Second generation axial pumps have an impeller outflow directly parallel to the axis of the rotation. The rotator spins on the mechanical or contact-free bearings like that of the HeartMate II. Third generations have impellers of outflow direct perpendicular from the axis to the rotation of that in the heartware in the HeartMate III. The design of the most recent pumps is the goal to be contact-free with no mechanical bearings and an impeller suspended using magnetic or hydrodynamic systems. I would like to discuss some of the screening that's done ahead of time, which we've alluded to earlier. Echocardiograms need to be done to evaluate the ejection fraction. VO2 testing needs to be done to make sure it's under that 14. A right heart cath looks at hemodynamics and cardiac output. Dental assessments are done to look for any source of infection. Pulmonary function tests are used to evaluate lung function, especially with being on a ventilator. Patient's labs are looked at for his renal function, liver problems, and looking at overall end organ function. And the goal is that the patient would have a life expectancy less than two years. Other considerations for a patient that's getting an LVAD is making sure there's education. A patient must be committed to follow-up and as well as lifestyle changes. An individual with an LVAD is not gonna be able to swim. They're gonna have to make sure that they carry their equipment and that they have extra batteries. Individuals are gonna need to be able to change batteries and maintain their equipment, as well as have meticulous self-care to decrease the risk of infection. Ventricular assist devices also rely on electricity, so the individual needs to have power or electricity at their home. Prescreening for an LVAD includes, as mentioned, is infection risk, making sure that there's not an active malignancy, looking at overall their mental health, and making sure there's no suicide ideations or risks. Once again, making sure that they have electricity as well as grounded outlets at home. The use of a telephone or way to communicate, a support system they're gonna need to support initially, especially as they're recovering from their surgery, as well as lifelong, and as well as the ability to learn the device as well as the medications. A complete psychosocial assessment is also done. The attempt is to decrease obstacles such as transportation, medication coverage, and willingness to seek help. Individuals are also evaluated by a PSYPAT, which is the Stanford Integrated Psychosocial Assessment for Transplant. This slide shows a little bit about the LVAD parts. You will note there's a dressing as well as a driveline, and this is where meticulous care comes into place. There's also batteries, as well as the controller for different devices. There's different components to an LVAD. The first we have is the speed. The speed indicates basically how fast the motor is going in the pump. The power is that of how much energy or watts the pump is consuming to get that speed. The pulsatility index is more of what the native heart is doing, noting that if the speed increase, the pulsatility index will go down. If the speed is decreased, the pulsatility index will go up. And if the preload increases, the pulsatility index will also increase. When the preload decreases, the pulsatility index will also decrease. The HeartMate 2 originally came out as destination therapy in January of 2010 and bred to transplant in April of 2008. The speeds for this pump are 8,000 to 11,000. Of note, this pump is not placed in individuals anymore, but there is individuals that still have this pump to this day. The HVAD, our HeartWare HVAD, is a centrifuge pump that has speeds of 2,400 to 3,500. Although the HVAD is not placed anymore due to the HeartMate 3, which we'll talk about shortly, being superior as far as related to strokes, the HVAD pump has a monitor which shows how the patient is doing. You can measure the patient's flow pulsatility, which is that of the difference of usually two milliliters per minute. You can also look at their peaks or troughs. For these individuals, it is easier to tell their volume status as well as if they are having any arrhythmias. The HeartMate 3 is a centrifuge pump that has speeds from 4,500 to 6,500. This pump is actually unique. Every two minutes, there's an artificial pulse mode. In the pulse mode, it is noted that there's a single rotator speed set. Every two minutes, the flow will drop so that there is native contractility of the heart. Once again, HeartMate 3 is the current pump that's being installed, noting that it was superior over the other LVADs due to decreased stroke risk. Some of the complications for an LVAD include that of aortic valve insufficiency, GI bleeds, pump thrombus, pump malfunction, stroke, infection, and arrhythmias. Warn you, the next slide is very graphic. In this slide that you will notice a stroke, driveline infection. In the dark urine, you'll notice that there's lysis of the red blood cells. And in the far right, you will see a clot that's actually an LVAD. Management of an LVAD, besides the education, the goal of the Doppler blood pressure is less than 85. I wanna talk a little bit more about management of an LVAD. Besides heart failure medication, the speed is looked at, power is looked at, and the PEI. Individuals will have serial echocardiograms looking at the LV and RV function as well as that aortic valve. Individuals need to be anticoagulated, usually on Coumadin, with a goal INR from two to three as long as they don't have complications such as bleeding or thrombus. I wanted to talk a little bit about pulsatility and continuous flow pumps. Even with this severely depressed heart, there's some residual contractility. As mentioned earlier, when preload increases in a native LV, the Starling curve is impacted and the pulsatility increases. When the preload decreases, the pulsatility decreases. In this way, we can see how well a patient's native heart is functioning. I wanted to talk a little bit about emergency procedures. Advanced cardiovascular support treatments can apply for LVADs, but it is discouraged within the first three months of VAD placement. When should a patient be considered for heart transplant? Individuals who have end-stage heart failure with severe symptoms, poor prognosis, and no remaining alternatives should be considered for a heart transplant. These individuals need to be motivated, well-informed, as well as emotionally stable. They also need to be capable of learning as well as complying with the complex medical regime post-operatively. Some of the exclusion criteria for that of a heart transplant include an active infection, those with peripheral vascular disease, individuals that are currently using drugs, alcohol, or smoking, individuals that are being treated for cancer, and especially any recurrent cancer within the last five years, individuals that have unhealed peptic ulcers, as well as recurrent thromboembolisms, individuals that have significant renal failure, liver failure, or other multi-organ failure. Other contraindications include that of individuals who have a poor overall prognosis and that have undertreated or instability related to their mental illness or high pulmonary pressures. This diagram shows that of the exclusion criteria for that of a heart transplant versus an LVAC. Noting as mentioned in a heart transplant, individuals cannot have a recent malignancy, high pulmonary vascular pressures, decrease in organ perfusion, age, the other consideration, noting that individuals need to be less than 70, as well as a BMI less than 35. Exclusion criteria for an LVAD, besides that of a poor social support, include that of restrictive cardiomyopathies, as such as a small ventricle, noting that if you put the LVAD in the ventricle, it will actually make their symptoms usually worse. Other contraindications include that of poor tolerance to anticoagulation, intractable angina, as well as intractable BT. Of the over 3,500 transplants that are performed yearly, it is noted that more than half of them are performed in the United States. The postoperative survival for a transplant is usually 15 years. This slide compares that from an LVAD to a transplant. Looking at an LVAD within the first year, the survival rate is about 56 to 87%. Note that over time, the percentage goes down. Within four years, the survival is about half. In a heart transplant, the one-year survival is noted about 80%. Three years goes down to 79, and at five years, we were looking at 69 and 73, depending on gender. These are my references for these modules. Thank you very much for your time.

sudden cardiac death prevention

advanced therapies

heart failure

implantable cardioverter-defibrillator

guideline-directed medical therapy

left ventricular assist devices

heart transplant