Evaluating and Treating a Patient With Heart Failure
In this podcast episode, Dr Harrison discusses evaluating and treating a patient with heart failure, including the types of heart failure, the pathophysiology, risk factors, and more.
For more heart failure content, visit the Resource Center.
Anil Harrison, MD, is the Program Director and Chair of the Internal Medicine Residency Program at the University of Central Florida and HCA Florida West Hospital (Pensacola, FL). Dr Harrison is board certified in India and the United States.
TRANSCRIPTION:
Jessica Bard:
Hello everyone, and welcome to Multidisciplinary Dialogue: Clinical Rounds and Case Reviews, with your host Dr Anil Harrison, who is the program director and chair of the Internal Medicine Residency Program at the University of Central Florida and HCA Florida West Hospital in Pensacola, Florida.
Today we have a case review that Dr Harrison will analyze and provide treatment insights. The views of the speakers are their own and do not reflect the views of their respective institutions or the views of Consultant360.
Dr Harrison, could you tell us a little bit about our patient today?
Dr Anil Harrison:
Yeah, absolutely. So Jessica, today we have a patient who's a 60-year-old with three days of worsening dyspnea on exertion, with a known history of non-ischemic cardiomyopathy, which was diagnosed three years prior with an ejection fraction of 30% and a GFR of 45, with a creatinine of 1.5. This patient's home medications include lisinopril, 10 milligrams a day; metoprolol, 25 milligrams a day; and Lasix, 40 milligrams twice a day. This patient's heart rate is 104, blood pressure is 94/64, is satting at 91% on room air. The JVD is to the angle of the jaw and one hears crackles at the bases bilaterally, along with 2/6 systolic murmur at the apex radiating to the axilla, but without an LV S3. The patient has warm extremities, has 2+ pitting pedal edema to the knees bilaterally, and the labs show a BNP of 530, a troponin which is normal, a creatinine which is 1.6, a BUN of 38, and a sodium of 136.
Jessica Bard:
Okay, well, before we go on to evaluating and treating our patient, it might be beneficial to discuss what is heart failure? The types of heart failure, the pathophysiology involved, and how should a physician go about the evaluation and management of the case in which you just mentioned?
Dr Anil Harrison:
Absolutely, Jessica. So heart failure is actually a term, which sounds extreme. It's a condition where typically one might get symptoms such as shortness of breath, swelling in the legs, fatigue, et cetera. And while examining the patient, we might find an elevated jugular venous pressure, or crackles at the bases of the lungs, or lower extremity edema. This is usually either because of a structural or a functional cardiac abnormality, which causes a reduction in the cardiac output or in the forward flow and/or elevated intracardiac pressures, causing a backlog of blood and fluids in the lungs and on occasion, throughout the entire body.
The clinical severity of heart failure is graded according to the NYHA, which stands for the New York Heart Association, on the basis of clinical symptoms at various degrees of physical activity of the patient. The American College of Cardiology and the American Heart Association introduced a classification which combines the clinical symptoms and the concomitant disease along with the risk factors to develop heart failure.
Jessica Bard:
How common is heart failure and what are the risk factors?
Dr Anil Harrison:
Yeah, that's a great question, Jessica. So the lifetime risk to develop heart failure is about one in five for a 40-year-old man in North America and in Europe, and it actually increases with age. The main risk factors are coronary artery disease, hypertension, diabetes, a family history of heart disease, obesity, chronic pulmonary diseases, inflammation or chronic infection, metabolic diseases, and treatment with certain cardiotoxic agents. Those are medications that are used for cancer therapy.
Heart failure is a progressive disease and it has an annual mortality of about 10%. The main causes of death are either sudden cardiac death, which happens in more than half the people, or organ dysfunction due to hypoperfusion.
Jessica Bard:
How does one categorize heart failure, and what is the difference between heart failure with preserved EF and heart failure with low EF?
Dr Anil Harrison:
Great question again, Jessica. About half of patients hospitalized for heart failure have heart failure with preserved ejection fraction, also called HFpEF, and they have an ejection fraction of more than 50%. The remainder of patients have heart failure with reduced ejection fraction, also called HFrEF, and the ejection fraction is less than 40%, or folks who have heart failure with mid-range ejection fraction, also called HFmEF, where the ejection fraction is between 41% to 50%. A common fact for these is the increasing incidence in high mortality.
Heart failure with preserved ejection fraction, called HFpEF, is characterized by structural and cellular alterations leading to an inability of the left ventricle to relax properly. Example, the cardiomyocyte, the hypertrophy, there is intercellular fibrosis, there is altered cardiomyocyte relaxation, and there is inflammation. HFpEF is also connected with chronic comorbidity such as hypertension, Type 2 diabetes, obesity, renal insufficiency, lung issues, liver issues, sleep apnea, gout, cancer, et cetera, et cetera, et cetera. And there's a lot of inflammation. There is increased oxidative stress resulting in an imbalance of nitric oxide or energy bioavailability. Patients with HFpEF are older and show a twofold predominance of females.
However, the predominance of men in heart failure with reduced ejection fraction, called HFrEF, might be connected to a higher incidence in myocardial infarction. HFrEF is characterized by a substantial cardiomyocyte loss, acutely or chronically, resulting in the development of systolic dysfunction. Example, myocyte loss following myocardial infarction, or it could be a genetic mutation or it could be a secondary to myocarditis, or it could be because of valvular disease, with cell death due to overload, followed by inability of the left ventricle to contract properly. Another difference between these two is with HFrEF, there is eccentric remodeling with excessive fibrotic tissue, whereas in HFpEF, there is a concentric cardiomyocyte hypertrophy.
Another way of categorizing heart failure depends on the side of the heart which is involved. With the left side, you call it left ventricular failure. If it's the right side, you call it right ventricular failure. And when both sides are involved, you call it biventricular failure. Left ventricular dysfunction, which could be volume or pressure overload, increases the pulmonary pressure, called backward failure. It increases the pulmonary capillary wedge pressure and consequently pulmonary congestion occurs, resulting in dyspnea and tachypnea. And of course, you can hear crackles as well.
As the peripheral circulation is reduced, called forward failure, renal dysfunction can occur, or other peripheral malperfusion and malabsorption of nutrition with the signs of cardiac cachexia may also develop. In a chronic state, the permanent activation of neurohumoral systems leading to further volume overload causing liver congestion, ascites, edema, peripheral vasoconstriction, increased heart rate at rest and during exercise, cause a further deterioration of the cardiorenal system. Overload, be it pressure or volume of the heart, leads to enlargement of the heart itself. And as a measure, the cardiothoracic index increases with leftward shift of palpable cardiac pulsations. Now mostly in volume overload situations, filling volume of the ventricle increases periodically, and a typical third or fourth heart sound called an LV S3 or an LV S4 gallop can also be heard. Heart failure therefore influences almost all organ systems, and thus heart failure is a systemic disease or a syndrome with a broad clinical spectrum. Of course, comorbidities such as anemia, iron deficiency anemia, kidney failure, diabetes, being frail, can make heart failure worse.
Jessica Bard:
Could you elaborate on the activation of compensatory mechanisms, since the treatment of patients with heart failure involves medications targeting these?
Dr Anil Harrison:
Yes, absolutely. So in order to do that, the understanding of the underlying pathophysiology of heart failure is very important. Extensive trivial evidence supports the use of guideline-directed medical therapy and device-based therapies for optimal management of patients with heart failure, with reduced ejection fractions only. To overcome the impaired metabolic situation, centrally the heart and peripherally following reduced cardiac function or increased cardiac load, severe compensatory mechanisms are activated. That is activation of neurohormonal systems such as the renin-angiotensin-aldosterone system, called the RAA, and the sympathoadrenergic system, as well as adaptive mechanisms on the cellular and molecular level. In consequence, the muscle sympathetic nerve traffic is increased in HFrEF, HFmEF, and HFpEF. Catecholamines also increase myocardial oxygen demand, predispose for life-threatening arrhythmias, and activate signaling pathways of hypertrophy and cell death. In consequence, cardiac function further deteriorates and is associated with adverse outcomes.
Therefore, it makes sense to use medications which counteract these neurohormonal mechanisms such as ARNIs, which stands for angiotensin receptor blockers neprilysin inhibitors; ACE inhibitors; mineralocorticoids; beta blockers. They all have been shown to decrease heart failure hospitalizations and improve survival, and are recommended for the treatment of all patients with current or prior heart failure symptoms, unless of course, contraindicated or not tolerated.
Adding mineralocorticoids such as spironolactone or eplerenone to ACE inhibitors or ARBs or ARNIs, along with beta blockers, is recommended in patients with NYHA functional Class II through IV heart failure who have left ventricle ejection fraction less than 35%, in order to reduce morbidity and mortality. In all symptomatic patients, diuretics are used to reduce preload and improve symptoms.
Jessica Bard:
Are medications the only way to treat patients with heart failure?
Dr Anil Harrison:
There are other interventions which are also used such as TAVI in aortic stenosis; TMVR, which is trans mitral valve repair, in mitral regurgitation; CRT, which stands for cardiac resynchronization therapy, in patients who have a left bundle branch block and chamber dyssynchrony; and surgical therapy options such as left ventricular assist devices or CABG, which may be performed to improve cardiac function via reducing preload or afterload, and also modulating neurohormonal activation.
Jessica Bard:
What does it mean to be at risk for heart failure and advanced heart failure?
Dr Anil Harrison:
That's a great question, Jessica.
At risk for heart failure, which means a person has risk factors for heart failure, though has not developed heart failure as yet, as opposed to advanced heart failure where the symptoms and/or signs for heart failure are profound. Therefore, it makes sense, if a person has risk factors to pay heed to them and hopefully prevent heart failure in the future.
Now, there are stages of heart failure and Stage A is at risk for heart failure, but without structural disease or symptoms of heart failure. These folks have the following. They either have hypertension, atherosclerotic disease, or diabetes or obesity or metabolic syndrome, or patients with a family history of cardiomyopathy or at risk for heart disease. And so the question is what do you do, when a patient is at risk for heart failure? So therapy would be, you follow a heart-healthy lifestyle, prevent vascular coronary artery disease, prevent left ventricular structural abnormalities in these patients by using ACE inhibitors, or angiotensin receptor blockers in appropriate patients, with vascular classes or diabetes, and to use statins as appropriate using the ASCVD risk calculator.
Stage B is structural heart disease. People already have something going on with the heart, but they don't have overt signs or symptoms of heart failure. So these could be patients who've had a previous MI or with left ventricular remodeling including LVH, which stands for left ventricular hypertrophy, and low ejection fraction, or folks with asymptomatic valvular disease, which means they've got issues with their cardiac valves, but they are not in heart failure as of now. In these folks, you would include goals to prevent heart failure symptoms, prevent further cardiac remodeling, by using ACE inhibitors or ARBs as appropriate. Beta blockers are also appropriate in selected patients and in very selected patients, you might want to consider ICDs or revascularization or valvular surgery, as appropriate.
Stage C includes structural heart disease with prior or current symptoms of heart failure. Patients with known structural heart disease, these can be divided having heart failure with reduced ejection fraction or heart failure with preserved ejection fraction. Folks with heart failure with reduced ejection fraction, the goal should be to control symptoms. Patient education is very important and prevent hospitalizations, and of course prevent mortality as well. And drugs for routine use would be diuretics for fluid retention, ACE inhibitors or ARBs, beta blockers, aldosterone antagonists, and drugs used in selected patients would be hydralazine along with isosorbide dinitrate and digitalis. In selected patients, also consider ICDs, CRTs, revascularization or valvular surgery as appropriate.
Stage D is refractory heart failure and patients with marked heart failure symptoms at rest who probably require recurrent hospitalizations despite guideline-directed medical therapy. Therapy in these folks should be to control the symptoms and improve the quality of life, reduce hospital readmissions, establish patient's end-of-life goals. This should include advanced care, heart transplant, chronic inotrope therapy, temporary or permanent MCS, experimental surgery or drugs, palliative care and hospice, and ICDs.
So advanced failure, when you see advanced failure, you know it. And one of the things that I use as a mnemonic, I NEED HELP. I stands for inotropes, N for NYHA Class the patient is, in their levels of BNP, the natriuretic peptide. E is for end organ damage and ejection fraction; D stands for defibrillator shocks, H for hospitalizations, E for edema, or when one has to escalate the dosages on the diuretics. L stands for low pressures and P stands for prognostic medications.
This helps prognostify a person with advanced heart failure and for NYHA IV, always think of palliative care, cardiac transplant, mechanical support, et cetera, et cetera.
Jessica Bard:
How does one go about the evaluation of a patient with heart failure?
Dr Anil Harrison:
That's a great question. If you take the sixty-year-old patient we discussed, with three days of worsening dyspnea on exertion with a known history of non-ischemic cardiomyopathy diagnosed I think three years prior, who had an ejection fraction of 30% and a GFR of 45 with a creatinine of 1.5. And the medications that the patient is on is lisinopril, 10 milligrams a day; metoprolol, 25 milligrams a day; Lasix, 40 milligrams twice a day; and this patient's heart rate is 104. The blood pressure is 94/64, the oxygen saturation being 91% in room air and the JVD is to the angle of the jaw and crackles are heard bilaterally. And this patient also has a 2/6 systolic murmur at the apex radiating to the axilla, but no LV S3. This person is warm, has 2+ pitting pedal edema to the knees bilaterally, and the labs show a BNP of 530, a troponin which is normal, a creatinine of 1.6, and a BUN of 38, and a sodium of 136.
So when evaluating a patient with heart failure, there are a few things that need to be determined. The number one thing is how sick is the patient? What is the cause for the decompensation? What medical therapy are you going to think about? And then you have to think about transition to discharge when the patient is stable. And then you have to think about, does this patient actually need any advanced planning?
So physical exam is very important, and evidence for a low perfusion would be things like narrow pulse pressure, cold forearms and legs. The patient might be sleepy or obtunded, the blood pressure might be low and declining serum sodium and/or worsening renal functions would be some of the things that you want to look for.
Now, evidence of congestion, on the other hand, would be that a patient has orthopnea, has an elevated JVD, might have an LV S3, a loud P2, could have ascites, and on occasion rales on auscultation.
When assessing the patient with heart failure, this is how one ought to think. Is the patient warm and dry, or is the patient warm and wet, or is the patient cold and dry? Or the extreme being, is the person cold and wet? So what is diagnostic value of exam? Why is this important? What is the event-free survival for this patient over the next one year?
Warm and dry scenario is the best, warm and wet, the second best, and understandably, cold and wet is the worst. While evaluating, besides considering warm and dry, having a better prognosis while cold and wet, having a worse prognosis, there are other predictors of in-hospital mortality such as your blood urea nitrogen, your creatinine, and what is the person's systolic blood pressure.
Let's take some examples. If the BUN is less than 43, the systolic blood pressure is more than 115 millimeters of mercury, the hospital mortality is 2.1%. But if the BUN is less than 43 milligram percent and the systolic blood pressure is less than 115, the in-hospital mortality goes up to 5.5%.
Now the question comes, what if the BUN is greater than 43 milligram percent? Then besides taking a look at the systolic blood pressure, one should also include the serum creatinine as well. If the BUN is greater than 43 and the systolic blood pressure is also greater than 115, while the serum creatinine is less than 2.75 milligram percent, the mortality is 12.4. But, if the BUN is greater than 43, the systolic blood pressure is less than 115 and the serum creatinine is more than 2.75, the mortality goes up to 22%. Therefore, there is a tenfold change in the in-hospital mortality based on three parameters which are BUN, creatinine and systolic blood pressure. This was actually published, I think in JAMA, in 2005.
Jessica Bard:
Dr. Harrison, what is the role of BNP?
Dr Anil Harrison:
Jessica, BNP, which is secreted by the ventricles in response to either pressure or volume overload, is increased in decompensated heart failure, although false negatives can occur in heart failure with preserved ejection fraction, HFpEF, and also in obesity. False positives of BNP can occur with chronic LV dysfunction or if a person has a PE or a person has cor pulmonale, and of course, if a person's kidneys are not doing the best. Renal dysfunction.
Jessica Bard:
Can you give us the pathophysiology of BNP, the RAAS system, and the medications with GDMT?
Dr Anil Harrison:
Yeah, absolutely. BNP causes suppression of renin, angiotensin, and endothelin, and therefore it results in decreased peripheral resistance and natriuresis, hence resulting in a reduced blood pressure. Measurement of baseline levels of natriuretic peptide biomarkers along with cardiac troponin, on admission to the hospital, is useful to establish prognosis in acute decompensated heart failure. However, targeting a certain threshold value or relative change in these biomarker levels during hospitalization may not be practical or safe for every patient and honestly, has not been tested in prospective large-scale trials.
The pathophysiology of BNP, they're disintegrated by neprilysin to inactive fragments. The natriuretic peptide occupy the natriuretic peptide receptors, causing a decrease in blood pressure, sympathetic tone, vasopressin, aldosterone, hypertrophy, fibrosis, and cause increase natriuresis and diuresis. So they're very beneficial.
On the other hand, angiotensin II occupies angiotensin receptors, causing just the opposite: vasoconstriction, increased blood pressure, increased sympathetic tone, excessive aldosterone, causing hypertrophy and fibrosis. Therefore, ARNIs act negatively on neprilysin and angiotensin receptors. To address the sympathetic nervous system where adrenaline occupies the alpha-1, the beta-1, and the beta-2 receptors, causing an increase in the heart rate and contractility. Therefore, it makes sense to use beta blockers for that. For the RAAS, which is the renin angiotensin aldosterone, you use inhibitors like ACE inhibitors or angiotensin receptor blockers and mineralocorticoid antagonists.
Okay, so now let's discuss our sixty-year-old with a history of non-ischemic cardiomyopathy, diagnosed five years ago with an ejection fraction of 30%, who presented with worsening dyspnea on exertion, and this person had a GFR of 45, with a creatinine of 1.5; while taking lisinopril, 20 milligrams a day; metoprolol, 25 milligrams once a day; and Lasix, 40 milligrams twice a day. And this person has a heart rate of 105, a blood pressure 90/64, oxygen saturation, 91% in room air and the JVD is elevated. There is no LV S3, and this person is warm with 2+ pitting edema in the lower extremities. This person's BNP was 550, troponin was normal, and a creatinine of 1.6, a BUN of 38. How do we proceed?
So this patient is wet and warm. The BUN is less than 43. This systolic blood pressure is less than 115 and the creatinine is less than 2.75. So with the patient being wet and warm, BUN being less than 43, systolic blood pressure less than 115 and the serum creatinine less than 2.75, this person's in-hospital mortality is about 5.5%.
After one establishes how sick the patient is, the next step is to find out what is the cause for this patient's decompensation. According to the ACC and the American Heart Association guidelines, acute coronary syndromes, precipitating acute heart failure, decompensation should be promptly identified by an EKG and serum biomarkers including cardiac troponin testing and treated optimally as appropriate to the overall condition and prognosis of the patient.
So the common precipitating factors for acute heart failure should be considered during the initial evaluation and there is a mnemonic for this, which is called FAILURE, where F stands for forgot medications. A stands for arrhythmias or anemia. I for ischemia, infarction or infection. L for lifestyle changes. U for upregulation of cardiac output and R for renal failure and E for embolism/pulmonary embolism. Forgot medication basically means non-adherence. So the person is taking things like non-steroidal anti-inflammatory medications or steroids or TZDs or beta blockers or calcium channel blockers. Changes with lifestyle include increased intake of salt, or the patient has started drinking excessive alcohol, or illicit drug use. Upregulation of cardiac output occurs with pregnancy or thyroid disease.
The question is, does the reason matter? The answer is yes. For example, if the decompensation is due to non-adherence of diet or uncontrolled hypertension, the mortality is 1.7% as opposed to, for example, if the patient develops a pneumonia as a cause for worsening heart failure, the mortality is about 5.8%. But if the renal functions are deteriorated, the mortality goes up to 8%. Similarly, acute coronary syndrome and infections carry a high 90-day mortality.
After evaluating how sick the patient is, then you have to figure out what is the cause for this person's decompensation, following which, what do you treat the patient with? So diuretics are important. Guideline-directed medical therapy, called GDMT, you think of inotropic support. Think of tips, tricks, and pearls.
Diuretics, in the DOSE trial, a comparison of low dose versus high dose, bolus versus continuous diuretics were studied. High dose diuretics were more likely to result in euvolemia in 48 hours. High dose diuretics resulted in greater net fluid loss, weight loss, and symptomatic relief from dyspnea. High dose diuretics, though, are more likely to have an increase in the creatinine by about 0.3 milligram percent.
Bolus versus continuous: bolus was more likely to require dose increase at 48 hours as compared to continuous infusion. However, the endpoints were very similar. So the bottom line, ostensibly, is there is no difference. Most prefer high dose continuous infusions of diuretics.
Jessica Bard:
What should the dose of the diuretic be? Should it be given as bolus or as continuous infusion?
Dr Anil Harrison:
Yes, that's a great question. So according to the ACC/AHA guidelines, it is a Class 1 recommendation with heart failure, patients should be promptly treated with intravenous loop diuretics, with the initial intravenous dose being equal to or greater than the chronic oral daily dose. And this can be given either as a bolus or continuous infusion. While doing this, monitor the intake and output, their daily weights, their vital signs, their renal functions, and their electrolytes. Diuretics have a Class 2a recommendation when diuresis is inadequate, intensify with either increasing the dose of the intravenous loop diuretic or you add a thiazide diuretic.
Another important point is, when targeting diuresis, the goal is to go from congestion to decongestion and freedom from clinical congestion, without any peripheral edema, without any rales, without any dyspnea on minimal exertion. There should be no hepatomegaly or congestive GI symptoms. There should be no orthopnea or bendopnea and the JVD should be less than six to eight millimeters of mercury, without a positive hepatojugular reflex.
Jessica Bard:
What are some reasons why adequate decongestion may not be achieved?
Dr Anil Harrison:
The common reasons for residual congestion could be either the person has a low cardiac output state or the person might have a dominant right heart failure or the patient might have poorly functioning kidneys. The person might have symptomatic hypotension or it could be limitations to the patient engagement in self-care.
Jessica Bard:
How does one monitor congestion?
Dr Anil Harrison:
So you follow the signs and symptoms of a patient, but also measure their intake and output. We have to entertain the patient's dry weight and rise in creatinine while doing this because for each 1+ edema, it equals about five pounds of weight. If the situation arises that the intake and output is negative two liters, but the weight is up two pounds, then you trust the weight. So furosemide drips, IV is one's friend. Sleep is important. The patient should not be urinating after 9:00 PM. And I do want to mention, potassium pills are awful. So if you want to replace potassium, try not to do them with pills. Instead, think of spironolactone at that point. The target, while diuresing, should be three to five liters of urine output. The more weight loss there is, the more fluid loss, and especially good if no change in creatinine.
Aggressive diuresis can actually lead to hemo concentration and more weight loss, more reduction in filling pressure, and better survival. Now if the urine output is between three to five liters, then you continue the current diuretic regimen. But if it's less than three liters, and let's say if the patient is on the same dosage of furosemide, let's say 80 milligrams of furosemide, the suggestion is you give 40 milligrams intravenous bolus along with five milligrams per hour of furosemide. But if the patient is on 80 to 160 milligrams of furosemide, you give 80 milligrams IV furosemide, along with 10 milligrams per hour continuous drip of furosemide, and think about adding five milligrams of metolazone.
If the patient is on, let's say 161 to 240 milligrams of furosemide, then you could consider giving 80 milligrams of furosemide bolus, along with 20 milligrams per hour of a continuous drip, and you add metolazone, five milligrams twice a day.
Now let's take a scenario. What if the patient is on more than 240 milligrams of furosemide? Then you give 80 milligrams bolus and you go up to 30 milligrams per hour of a continuous drip and add five milligrams twice a day of metolazone.
Jessica Bard:
What if while diuresing, the renal functions deteriorate?
Dr Anil Harrison:
That's a great question, Jessica. Of note, worsening renal function alone in acute heart failure is not bad. With worsening renal failure plus no congestion, there is no impact on survival, although worsening renal function along with congestion does affect survival. Similarly, a drop in blood pressure plus worsening renal function, there was no impact on survival, but no drop in blood pressure plus worsening renal function. There was a worse survival. This was published in the European Journal of Heart failure in 2011.
Therefore, our patient with non-ischemic cardiomyopathy with an ejection fraction of 30%, creatine of 1.5, a GFR of 45, who was wet and warm, one could give furosemide a hundred milligrams intravenously twice a day or furosemide, 20 milligrams per hour with spironolactone, 12.5 milligrams once a day, and the plan being to increase it to 25 milligrams once a day.
Jessica Bard:
When should beta blockers be initiated?
Dr Anil Harrison:
That's a great question, Jessica. So the ACC/AHA guidelines for GDMT, one should initiate beta blockers after optimization of volume status and successful discontinuation of intravenous diuretics and inotropic agents. That is a point when you add a beta blocker.
Jessica Bard:
Should beta blockers be withheld or stopped?
Dr Anil Harrison:
Withholding of, or a reduction in beta blockers should occur only after recent initiation or an increase or with marked volume overload or marginal cardiac output.
Jessica Bard:
What should one do if renal functions worsen with RAAS antagonists?
Dr Anil Harrison:
Yeah, this does happen. So patients with significant worsening of renal function should be considered for a reduction or a temporary discontinuation of the renin-angiotensin-aldosterone antagonists until the renal functions improve.
Jessica Bard:
What are the elements of GDMT?
Dr Anil Harrison:
So the elements are for NYHA I through IV, ARNIs would be the first choice. You could use ACE inhibitors if you don't get an ARNI, or you could consider ACE inhibitors if the patient is ARNI-intolerant. Similarly, angiotensin receptor blockers could be used if ARNI-intolerant and ACE inhibitor-intolerant. And also beta blockers are recommended for NYHA Class I. Therefore, these medications should be included for NYHA I through IV. The question is, there's another great medication they call SGLT2 inhibitors, whether they should be, they're definitely used for heart failure and it's been proven that they help survival and they help also with heart failure and in folks who've got a compromise in the renal functions. So they're great medications.
The other thing is for NYHA II through IV, spironolactone should be the next medication. Another medication called ivabradine. One could use that if the heart rate is greater than 70 and the patient is on normal sinus rhythm, on maximum tolerated beta blockers. Another thing to consider is cardiac resynchronization therapy, if the person is in normal sinus rhythm and has a left bundle branch block. You also have to consider a defibrillator as well.
For NYHA III to IV, isosorbide dinitrate along with hydralazine, especially if a person is of African-American descent. Another medication you could use, digoxin, especially if the patient is still symptomatic. When a patient is NYHA four, then you have to consider things like cardiac transplant, mechanical circulatory support, also called MCS, and, of course, consider hospice as well.
Jessica Bard:
You mentioned ivabradine. What is this medication and when should one consider using it?
Dr Anil Harrison:
Sure, Jessica. Ivabradine inhibits the 1F in the pacemaker cells of the SA node, causing a decrease in the heart rate without causing a decrease in the contractility. They've been some thought about questionable improvement in the outcomes and heart failure from the SHIFT study. Comparing ivabradine to placebo in 6,500 patients with reduced ejection fraction less than 35%, and a heart rate more than 70, who had one heart failure hospitalization, and were on maximum tolerated beta blockers. Outcomes were heart failure, deaths reduction was from 5% to 3%, and in the heart failure hospitalizations, there was a reduction from 21% to 16%. Ivabradine is a Class 2A medication. Ivabradine can be beneficial to reduce heart failure hospitalizations in patients with symptomatic NYHA II through III, stable chronic heart failure with reduced ejection fraction less than 35% who are receiving a beta blocker at the maximum tolerated dose and who are in sinus rhythm and the heart rate is more than 70 at rest.
Jessica Bard:
Why not just give neprilysin inhibitors alone? Why is it combined with an ARB and why not combine it with an ACE inhibitor?
Dr Anil Harrison:
Great question, Jessica. As discussed in the pathophysiology earlier, neprilysin also degrades angiotensin. If you use a neprilysin inhibitor, it would actually increase the levels of angiotensin, causing adverse remodeling. So neprilysin inhibitors plus an ACE inhibitor is a bad idea. Why? Because neprilysin degrades bradykinin as well. So neprilysin inhibitors would increase bradykinin levels, and so using it with an ACE inhibitor would cause increased bradykinin levels and this could actually result in angioedema. And so that is the reason neprilysin inhibitor is combined with an ARB.
Jessica Bard:
Could you speak about the benefits of ARNIs?
Dr Anil Harrison:
In a study with heart failure taking 8,400 patients, and I think the study was PARADIGM, P-A-R-A-D-I-G-M. And so these patients with reduced ejection fraction who had one heart failure hospitalization with elevated BNP sacubitril/valsartan, which is an ARNI, this was compared with enalapril, which is an ACE inhibitor. The outcomes in the cardiovascular deaths were reduced from 17% to 13%. Heart failure hospitalizations reduced from 16% to 13%, with a hazard ratio of 0.80, confidence interval of 95%, P-value less than 0.01.
Jessica Bard:
What does one do when someone is already on an ACE inhibitor?
Dr Anil Harrison:
So if somebody is on an ACE inhibitor, it is advised to hold the ACE inhibitor for at least 36 hours before instituting an ARNI. And why is this? This is to take the bradykinin as a factor. You want to give at least a three-day break when you consider switching a person or replacing an ACE inhibitor with an ARNI. In 2016-17 Heart Failure Focused Update, ARNIs have a Class 1 recommendation for folks with heart failure. Similarly, ACE inhibitors or ARBs or ARNI in conjunction with beta blockers and aldosterone antagonists are recommended for patients with chronic heart failure, to reduce morbidity and mortality.
The recommendations are in patients with chronic symptomatic heart failure with reduced ejection fraction, NYHA Class II or III, who tolerate an ACE inhibitor or an ARB, replacement by an ARNI is recommended to further reduce morbidity and mortality. However, ARNIs should not be administered to patients with a history of angioedema.
Jessica Bard:
What about aldosterone antagonists?
Dr Anil Harrison:
Aldosterone antagonists are recommended for NYHA Class III through IV, and in a person who has an ejection fraction of less than 35%, or in NYHA Class II with prior hospitalization or with an increased BNP. You could also use it following an acute MI in patients who have an ejection fraction of less than 40% and have heart failure symptoms or if they have diabetes. It has a Class 3 recommendation. Do not use if the creatinine is more than 2.5 or if the GFR is less than 30, or if the potassium is more than five milliequivalents per liter. This is very important.
If somebody has a GFR that is less than 30 or a potassium more than five, try not to use aldosterone antagonists. If you do, then you check the potassium after two to three days and then in one week, and then you check it monthly for about one to three months, and then every three months making sure that the creatinine and the potassium are stable. Aldosterone antagonists cause a reduction in mortality. Now we've seen this, on occasion, patients who are on spironolactone, they develop gynecomastia. In that scenario. You switch to eplerenone, though again, you watch a person's potassium.
Jessica Bard:
What is the role for Isordil and hydralazine?
Dr Anil Harrison:
Isordil and hydralazine are definitely not as good as ARNIs, nor ACE inhibitors, or ARBs, nor should they be given in place of these medications. However, Isordil and hydralazine could be a consideration in African Americans or folks who are intolerant to ARNIs or ACE inhibitors or ARBs. This could also be as an add-on after the three categories of four categories of medication, including the beta blockers, the ACE inhibitors, the ARNIs, the spironolactone, and the SGLT2 inhibitors have already been utilized. So this could be an add-on.
Jessica Bard:
Can we speak about the role of SGLT2 inhibitors?
Dr Anil Harrison:
Yeah, so you know this SGLT2, which stands for sodium-glucose transporter-2 inhibitors offer cardiorenal protection. Recent results in non-diabetic experimental chronic kidney disease models, SGLT2 inhibitors, they cause glycosuria and they cause natriuresis. So glycosuria helps with better glycemic control and weight loss, and natriuresis causes blood pressure lowering, tubular glomerular feedback, amelioration of volume overload. And this results in intraglomerular pressure reduction, which is very important. So a combination of natriuresis and glycosuria are cardiovascular protective. This medication reduces oxidative stress, reduces fibrosis, local inflammation, tubular senescence, and glomerular damage. And we have enough data now that even in folks who do not have diabetes, SGLT2 inhibitors help prevent that from cardiovascular etiologies as well as hospitalizations in folks with heart failure. So reduction in cardiovascular death from 9.6% versus 11.5%, heart failure hospitalization from 10% versus 13%. This was published by McMurray et al in the New England Journal of Medicine in 2019. There was another study, the EMPEROR study, which showed that using SGLT2 inhibitors did show a reduction in mortality.
Jessica Bard:
Can we talk about a reduction in mortality with each class?
Dr Anil Harrison:
Sure, Jessica. When no therapy was given, your mortality was 35%. When ARNIs were added, the relative risk reduction by 28%, the two-year mortality went down to 25%. When beta blockers were added, the relative risk went down by 35%. The two-year mortality went down to 16%. When aldosterone antagonists were added, the relative risk went down by 30% and the two-year mortality reduced to 11.5%. When SGLT2 inhibitors were added, the relative risk lowered 17% and the two-year mortality went down to 9.5%. Hence, the importance of the use, be it ARNIs, ACE inhibitors, angiotensin receptor blockers, beta blockers, aldosterone antagonists, as well as the SGLT2 inhibitors. It's been demonstrated very well.
Jessica Bard:
What does one do if there is initial improvement, but then things get stalled?
Dr Anil Harrison:
If things do not improve, the idea is do not give up. Change your course, escalate the diuretics, consider other decongestion strategies. Consider hemodynamic monitoring. That is a time that you consider inotropes and also consider advanced therapies.
Jessica Bard:
Can we talk about instances when the patient is in cardiogenic shock?
Dr Anil Harrison:
Yeah, absolutely. When a patient is in cardiogenic shock, the cardiac output is reduced. Your mean arterial pressure, called MAP, is also reduced. And in order to maintain perfusion, your SVR, your systemic vascular resistance, is increased since MAP equals cardiac output times SVR. The thing to remember is that diuretics will not work until the [inaudible 00:46:55] output is taken care of. Therefore, one must use inotropes and vasodilators and warm up the patient before diuresing. There is Grade 1 evidence for monitoring with a pulmonary artery catheter in these patients, and it should be performed in patients with respiratory distress or impaired systemic perfusion, when clinical assessment is inadequate. Therefore, insert, or ask your friendly cardiologist to insert, a pulmonary artery catheter if there is volume overload and hypertension or volume overload plus renal dysfunction.
The inotropes that can be used could be milrinone or dobutamine or dopamine. But remember, half-life of milrinone is two to four hours, whereas dobutamine is two minutes and dopamine is one minute. All three of them cause increased intracellular calcium. Milrinone acts via the phosphodiesterase inhibitor, dobutamine acts via adrenergic beta-1, greater than beta-2 receptors, agonists greater than alpha-1 receptor agonist. Dopamine is adrenergic and dopaminergic agonist.
Jessica Bard:
What are some of the important points when discharging a patient with heart failure who has achieved the dry weight?
Dr Anil Harrison:
Transition to discharge, fluid balance is harder to achieve at home, so one has to be more aggressive, and it's very important to watch, especially in the first 24 hours on oral regimen of diuretics. And it is important that a phone call should be given to the patient. Hence, a discharge weight should be mentioned and bolded in the summary. With a phone call, the body weight, the intake and output, if possible. Does the patient have any symptoms, should be accounted for and labs ordered accordingly.
The very important thing is the patient should have an inpatient visit within one to two weeks because 25% of heart failure patients will be readmitted within 30 days of discharge. This is a time that we should all reconcile the medications, do labs, check renal functions and electrolytes, and before hospital discharge, at the first post-discharge visit, and in the subsequent follow-up visits, the following should be addressed. Initiation of GDMT, if not done, or for some reason it was contraindicated. What are the causes for heart failure? What are the barriers to care? What are the limitations to support? Assessment of volume status and blood pressure with adjustment of heart failure therapy, optimization of chronic oral heart failure therapy should be done. Renal functions and electrolytes should be measured. Management of comorbid conditions, heart failure education, self-care, emergency plans, adherence, palliative, or hospice care. So these things are very important.
Jessica Bard:
Now let's summarize and discuss folks with advanced heart failure.
Dr Anil Harrison:
Sure. So episodes of heart failure mark a fundamental change in heart failure trajectory. Patients admitted with heart failure have a 20% to 30% risk of death within a year. For patients with marked heart failure symptoms, recurrent hospitalizations despite guideline-directed medical therapy, the goal should be to control symptoms, improve quality of life, reduce readmissions, and establish end-of-life goals.
Now, options include heart transplant, palliative care and hospice, temporary or permanent MCS, and experimental surgery or drugs. In advanced heart failure, you know it when you see it. For years, patient can be in NYHA I through III. However, when they get to NYHA IV, there is a rapid decline. So the key questions are, what are the main components of effective inpatient heart failure care, which are prior to discharge? What therapies can an internist order to have the greatest impact on heart failure patients, the readmission rates, quality of life, and survival? When should the patient be referred for advanced heart failure therapies?
In those circumstances, consider the mnemonic I NEED HELP. I stands for inotropes, N for NYHA class or the natriuretic peptide, E for end organ damage, another E for ejection fraction, D for defibrillator shocks. H for how many hospitalizations has the patient had, E for edema and also escalating diuretics, L for low pressures and P for prognostic medications. So these are very important and need to be considered in these patients.
Jessica Bard:
Are there any other considerations for folks with heart failure?
Dr Anil Harrison:
Yes, some are being investigated such as parasympathetic nervous system stimulation, sildenafil, hawthorn extract, myotropes such as omecamtiv mecarbil, hormones like testosterone and growth hormone, stem cell transplant. Similarly, gene therapy, immunosuppressive therapy, thalidomide, pentoxifylline, intravenous immunoglobulin, counterpulsation and cardiac contractility modulation. Serelaxin is another one. Ularitide is another one. But more evidence is needed to make a decision before considering these.
Another one is Coenzyme Q10. Although a multi-center randomized trial found that Coenzyme Q10 therapy reduced mortality and hospitalization in patients with moderate to severe heart failure, further data is needed to establish the efficacy and safety of Coenzyme Q10 therapy in patients with heart failure.
Jessica Bard:
Dr. Harrison, that brings us to the end of the episode today. I appreciate your time. I think we learned a lot about the management of patients with heart failure. Thank you for joining us.
Dr Anil Harrison:
Thank you so much, Jessica. It was a pleasure. Bye-bye.
Jessica Bard:
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