Heart Failure + Diuretics with Dr. Justin Vader

An Interview between Harrison Lancaster MD and Justin Vader MD MPH FACC  

Edited by Mustafa Husaini MD MBA FACC 

Initial presentation: 

1. Generally, what does the term “Heart Failure” mean to you? What terminology do you use to classify patients with a diagnosis of heart failure (i.e., acute vs. chronic, compensated vs. decompensated, reduced vs. preserved vs. recovered) and why is this terminology important for medicine residents to understand? 

Historically, heart failure was considered  a condition where the heart cannot deliver oxygen at a rate commensurate with the the requirements of metabolizing tissues (I.E. elevated lactates). As studies have demonstrated that a large proportion of heart failure patients have normal lactates, an updated universal definition of “Heart Failure” that was published in the journal of Cardiac Failure a few years ago. That definition describes “Heart Failure” as a clinical syndrome with signs or symptoms caused by structural or functional abnormalities of the heart which is associated with elevated natriuretic peptide levels and/or objective evidence of pulmonary or systemic congestion. A conceptual basis of the Universal Definition of Heart Failure is below.  

Cleland Eur Heart J. 2021 Jun 21;42(24):2331-2343. 

We typically think of these characteristic signs and symptoms as shortness of breath (which can be positional and/or exertional), paroxysmal nocturnal dyspnea, lower extremity edema, and fatigue. The abnormalities in cardiac function that cause these symptoms can be abnormalities in systolic function or diastolic function, which is typically assessed via echocardiography. These signs and symptoms are also typically associated with signs of elevated intra-cardiac filling pressures. These intra-cardiac pressures can be measured via a right heart catheterization or by cardiac biomarkers (NT-pro BNP), as mentioned in the universal definition, or can be implied by diastolic parameters on echo. 

When we use terminology to classify patients with Heart Failure, it is done predominately to distinguish which therapies will be most effective for each patient group. Heart Failure with reduced ejection fraction (HFrEF) is defined by a left ventricular ejection fraction (LVEF) less than 40%. Heart Failure with midrange ejection fraction (HFmrEF) is when the LVEF is between 40-50%, and Heart Failure with preserved ejection fraction (HFpEF) is when the LVEF is greater than 50%.  

There is a spectrum of response to neurohormonal antagonism via medical therapy (What we refer to as Guideline Directed Medical Therapy [GDMT]) for each subgroup of heart failure patients. Most of the large scale clinical trials on medical therapy for heart failure tells us that patients with HFpEF have limited response or improvement in their clinical symptoms, patients with HFmrEF can show a modest response, and patients with HFrEF can have marked response.  

It is also important to understand that the left ventricular ejection fraction, which is a tool that is used to classify these patients, can vary from test to test and reader to reader. So it is generally good to describe patients using these categories, although with the understanding that patients may not always be in one category during the course of their disease.  

Lastly, the terms acute, chronic, and acute on chronic as well as the terms compensated and decompensated are helpful to know. The former aids both in assessing the chronicity of symptoms (and thus potential etiology) while also being part of the administrative nomeclature that is needed to ensure reimbursement is consistent with the level of care we provide. The later terms help provide a lens on what our active goals of treatment are. When patients are compensated, the primary goal is to treat disease progression while when patients are decompensated, the primary goal is symptom relief.  

2. What are aspects of the history and physical exam that help you decide that a patient is having an acute decompensated heart failure episode? (Including labs/imaging/exam)  

I think it is first important to understand what symptoms patients typically have at rest and with exertion. If a patient is coming to the hospital for decompensated heart failure, it is typically because their symptoms have gotten markedly worse and are now present at rest. The characteristic symptoms of acute decompensated heart failure are breathlessness with minimal activity, orthopnea, paroxysmal nocturnal dyspnea, and lower extremity edema. Some other symptoms that patients with ADHF can have that often escape notice from younger physicians are abdominal fullness, early satiety, or anorexia. In extreme cases for patients who have very poor systolic function and are evolving into cardiogenic shock, altered mental status can be an associated symptom.  

 On exam, I think it is very important to focus on signs of congestion and perfusion. In terms of perfusion, I always feel the lower extremities to assess how warm or cold they are. Lower extremity mottling and acrocyanosis can be signs of poor perfusion. In terms of assessing someone’s volume status, obviously you will want to assess for lower extremity edema, but remember not to just look at the legs. You will also want to look for signs of jugular venous distention, particularly with provocation with the hepatojugular reflex and/or using the veins in the arm to confirm your estimated level of JVD . In terms of auscultation, an S3 gallop can be present in patients elevated cardiac filling pressures, but can often be difficult to hear given how noisy the hospital can be. Listening for rales can also be helpful, with the important caveat that not all patient with decompensated heart failure with have rales or radiographic findings of pulmonary edema. Patients with chronic heart failure have lymphatic hypertrophy that allow them to efflux fluid from the lungs at a higher rate than patients without heart failure. So just understand that it is possible to have elevated left heart filling pressures without overt evidence of pulmonary edema when completing your exam.  

3. How important is it to identify triggers of ADHF episodes? Could identifying particular triggers change management?  

Eliciting why patients are decompensated is certainly useful. I will try to understand if medication barriers (e.g., cost, transportation, pharmacy availablity, etc) or communication barriers (e.g., health literacy, clinian time to explain relationship between HF & GDMT)  is playing a role. Indiscretion regarding sodium and fluid intake can also be triggers for patients. Arrythmias are another common trigger for heart failure episodes, so I will often ask patients if they have experienced recent palpitations or have a history of atrial fibrillation as we see that pretty commonly in the hospital. I also look at the patient’s recent clinical history and think about them as a whole. Anemia, for example, can make the baseline symptoms of heart failure even more pronounced and could be a reason why a patient comes to the hospital. Obviously other clinical features like recent infections, prednisone use, etc can play a role as well.  

One of the most important triggers to identify would be ischemia. It is very important to ask patients if they have been having recent chest pain and to obtain an EKG on presentation to look for new signs of ischemia.  

Understanding why someone has chronic heart failure can also give you information about why someone has acute heart failure. If someone has longstanding severe heart failure, and has had multiple other hospitalizations for the disease, that is important to know. Sometimes a patient’s acute hospitalization may not represent a new acute problem or “trigger”, but may just be the natural progression of their disease. These patients are important to identify, as they often need more than just medications and may need to be evaluated for “advanced therapies”, which are things like a heart transplant, mechanical heart pump (LVAD), or a palliative assessment. Acute decompensated heart failure is an episode of chronic heart failure.  

4. Let’s say you are concerned that a patient is having a de novo heart failure event (HF not previously diagnosed), how do you think about these patients differently?  

So everyone that gets admitted for new onset heart failure will undergo a similar series of test, all geared towards trying to determine the underlying cause of that patient’s heart failure. These tests are typically; serum chemistries, natriuretic peptides, troponins, EKG, Chest X-ray, and echocardiogram. For patients with reduced left ventricular ejection fraction with any suspicion for coronary ischemia, you will typically get an assessment of that. The way in which we assess for coronary disease in these patients has been evolving over the years. I typically pursue left heart catheterization to do this. This will obviously give me information about a  patient’s coronary arteries, but you can also derive a left ventricular end diastolic filling pressure (LVEDP) during a LHC which can be helpful in determining how elevated a patient’s intra-cardiac filling pressures are. There are other ways to assess for this, like with a Coronary CT angiogram (CCTA) or nuclear perfusion testing (SPECT); a patient’s age, risk factors, family history, cardiac rhythm, and symptoms will determine which modality is likely best for them. 

I think it is also important to assess which patients may have other potential causes of cardiac dysfunction. For example, younger people who may have a history suggestive of an underlying inflammatory disorder or possibly myocarditis. These patients typically get additional testing with a cardiac MRI. For patients with conduction system abnormalities with new onset heart failure, I always entertain the notion that they may have an infiltrative process, like sarcoidosis. A Cardiac PET scan may be an appropriate test for those patients. For any patient with a strong suspicion of myocarditis, you should at least consider an endomyocardial biopsy. This would typically be done in concert with the advanced heart failure team. I typically get worried about Myocarditis when I see patients with rapidly progressive cardiomyopathy presenting with a lot of arrythmias. Furthermore, sometimes an echocardiogram or serum tests may raise your suspicion for amyloidosis, which is becoming commonly diagnosed as a cause of infiltrative cardiomyopathy. We have a special type of scan called a PYP (pyrophosphate) scan that can look for evidence of TTR amyloidosis.  

So most patients will get that initial series of tests to determine the severity of their cardiomyopathy and if it is ischemia driven. Then, additional testing is usually driven by your clinical suspicion for the underlying cause of their cardiomyopathy.  

Diuresis:  

1. The first thing most people think about when treating acute exacerbations of heart failure is diuresis – how do you go about selecting initial diuretic therapy? (DOSE trial, IV vs. PO)  

So it all starts with the volume assessment when I am first evaluating the patient. I often will try to gauge how much extra fluid I think a patient has, and then understand how naïve they may be to diuretics before deciding how much to give them. Although, there are some general rules of thumb when starting a patient on diuretics to be aware of as well.  

For patients who are furosemide naïve, a 40 mg IV dose will reach their diuretic ceiling. For patients who are on home loop diuretics, or we think may be diuretic resistant, we have to think a little more.  

A good starting point is usually taking the patients home dose of PO diuretics, doubling it, and giving it intravenously. For example, if a patient is taking furosemide 40 mg PO at home, I will start with giving them furosemide 80 mg IV in the hospital and monitor their response, with the expected early response being in 2-3 hours. Then, a decision needs to be made after that early response period on what dose should be given in the early afternoon; the up-titration of diuretics should happen much more frequently than daily.  

I also have a pretty low threshold for using continuous diuretic infusions in the hospital because I think this prevents doses of diuretic from being held for minor fluctuations in blood pressure or creatinine, which I see often. With that, however, there are concerns with continuous infusions such as increasing the risk of delirium and historical studies demonstrating structural remodeling of nephrons when exposed to continuous loop diuretics.   

The DOSE trial was a randomized clinical trial that showed no difference in short-term outcomes when using continuous diuretic infusions vs. bolus dosed diuretics. Thus, I think it is reasonable to use either strategy, however, I prefer continuous infusions due to the simplicity and that patients on them are less likely to inappropriately miss doses. 

 I also think beginning with the end in mind can be helpful when adjusting diuretic dosing. If I think a patient has 20 pounds of excess fluid on them, I try and think about how net negative I need to get them for how many days to get them back to their dry weight. This will give you some perspective when to escalate and de-escalate diuretic dosing. If a patient is net negative 1 Liter over a 24-hour time period, and they have 20 pounds to go, then that means they will likely need 20 days to get to their dry weight on that regimen and you likely need to escalate. I like to aim to at least net negative 4-5 Liters a day if I can to help expedite the process. That usually will not cause low blood pressure or kidney injury if the patient is truly volume overloaded. This is again why it is important to work on your physical exam to assess volume status. 

The most important aspect of diuresis to me is that patients are diuresed enough. Leaving patients under-diuresed has been shown to be associated with re-hospitalization, which is in nobodies’ best interest.  

2. For our audience who will be presenting on rounds – what are important factors to consider when determining how a patient is responding to diuresis? (improvement in exertional symptoms, exam, UOP, daily weights, changes in labs, etc.)  

I think weight change, urine output, patient symptoms, and markers of volume overload on exam are all important to report. An exceptional but time-consuming factor is seeing and/or knowing how much more functional the patient is every day; in other words, are they able to walk further in the hallway without getting fatigued or dyspneic. This gives us a much better sense of how they will be able to perform their ADLs after discharge as well as minimize the risk of under-diuresis (patients will come back to the hospital if/when they are symptomatic when doing their ADLs). Finally, ambulating helps mobilize third-spaced fluids so it’s a win-win situation.  

Understanding the context of a patient’s renal function and electrolytes are important as well. I will want to know if a patient is having electrolyte imbalances or significant creatinine elevation that may prevent further aggressive diuresis. Contraction alkalosis on a metabolic panel can also tell you if a patient is responding to diuresis or starting to dry out. Also, it’s important to keep in mind where the patient is in the context of the diuresis goal and in the context of their chronic heart failure. Some patients with severe chronic heart failure will develop cachexia and their true dry weight may be much lower than their suspected or previously recorded dry weight. We don’t trend daily BNPs, although sometimes it can be useful in a long hospital course to check a BNP to compare to the admission value to check your progress.   

3. How useful are fluid balance goals in the inpatient setting? Is it better to simply diuresis as much as possible each day while patients are being monitored? 

I think it depends on how much fluid a patient may have to diurese. I think if patients are very volume up, then your goal should really be to diurese them as much as you can. It is very rare than I regret diuresing someone too much if they truly have a lot of volume than needs to be mobilized. I think when patients are closer to euvolemia, then I think exercising caution with fluid balance goals can help make sure you don’t overshoot your mark.  

4. When is an appropriate time to consider adding additional nephron blocking agents such as Metolazone, Acetazolamide, spironolactone, and SGLT2 inhibitors?  When do you think residents should consider inotropes to assist with diuresis? 

I usually use these medicines when we are not meeting our diuretic goals for someone and they remain fluid overloaded. There are patients who can become refractory to loop diuretics because they have been on them for a long time. For these patients, I usually will add a thiazide diuretic like metolazone for additional diuresis. There are also patients who are chronic retainers of cardon dioxide and have a high bicarbonate who may benefit from being on acetazolamide (Diamox) in addition to a loop diuretic. Other agents I think about adding with diuresis are vaptans. Patients can get very hyponatremic when they are being diuresed, as they are losing sodium rich fluid and often drinking free water. Vaptans can prevent worsening hyponatremia and/or large sodium shifts, which can obviously be very helpful in these quite sick patients.  

The key thing to remember with all of these agents is that they can often worsen electrolyte changes and renal function so we need to be very diligent when utilizing them.  

I usually look for these agents to assist with diuresis before jumping to inotropes. I think about using inotropes in patients who have a paradoxically worse response to diuretics when I feel confident they are truly volume overloaded. For example, a patient that is very volume-up that, with IV loop diuretics, gets hypotensive or starts developing renal failure. These are signs that are concerning for very poor systolic function and need to be taken very seriously.  

Spironolactone is a good medication to consider because patients with heart failure should be on spironolactone anyway. Patients with HFrEF and HFpEF can derive a benefit with this medication. It can very useful in the context of diuresis as spironolactone can “counter-balance” hypokalemia associated with loop diuretics. I reach for this medicine often regardless of how well patients are responding to diuresis. The key to remember here is that spironolactone at low doses often does not have much of a diuretic effect.  

SGLT-2 inhibitors are medicines that can also be started during an acute hospitalization. IMPULSE was a study that looked at this (starting during an admission) in an organized way and showed a net benefit to doing so. My only word of caution regarding these medicines is that they are associated with an initial rise in the creatinine, that does not represent a decline in renal function. This effect can sometimes cause confusion, especially if these medicines are started while you are diuresing someone because you may not be able to sort out if a rise in the creatinine represents kidney injury or not. If you are worried about this confusion, then I would save the addition of a SGLT-2 to the end of a hospitalization or as an outpatient.  

5. Our patient is approaching euvolemia and we want to get them ready for discharge – what strategies to you recommend for transitioning to PO diuretics? Do all patients need to be “watched” on oral diuretics while still admitted? Do all patients need diuretics on discharge? 

I think this is where taking a good history will come into play. If a patient was taking their diuretics each day prior to their admission and still came in volume overloaded, then yes I think they should be discharged on more diuretics then they came in with. If the patient came in volume overloaded because they didn’t have access to their medications, or there is some other social barrier or cause to their symptoms, then I don’t think you should necessarily change their existing dose. I do think that patients who have been on furosemide for a long time will eventually see a diminished response to it, so that is something to take into consideration as well.   

Another thing to consider is where a patient retains a lot of their excess fluid. Some patients will have gut edema which can interfere with the absorption of furosemide. These patients may benefit from a switch to torsemide or bumetanide (bumex) for better absorption. The TRANSFORM study showed that there wasn’t a significant difference in the routine use of torsemide over furosemide, although I still find that I see clinical benefit in making this switch in select patients.  

I do like to observe patients for 24 hours on PO diuretics prior to discharge, if possible. However, I will also consider how closely someone can be followed up in the outpatient setting to determine if they truly need this. If a patient will be able to be seen within a week of discharge and I feel confident the patient will make it to that appointment, then I will feel more confident discharging them more expeditiously without that “watching” period. Otherwise, I think this can give you and the patient some security because your goal is to prevent them from coming back to the hospital.  

6. What other clinical pearls/practical tips do you have for medical residents about diuresis? 

It is important to remember that heart failure is a progressive chronic illness. When a patient does get admitted for a heart failure exacerbation, you obviously want to diurese them to help alleviate their acute symptoms, but you also want to ensure you are helping that patient in the long term. Diuretics are necessary for treating heart failure, but they don’t provide the mortality benefit that GDMT does. I think keeping that perspective is critical.  

Also, I think it’s important to be careful in using minor fluctuations in creatinine and potassium as being a determinant if patients can tolerate certain medicines. Sometimes we label patients as “intolerant” to medications because of a minor lab abnormality that occurred one time, which could mean those patients missing out on the significant benefits of that medication.  

On the flip side of that, if a patient is truly intolerant to GDMT and is having repeat admissions for heart failure, then think about that to. The traditional strategy may not work for that patient and they may need to be evaluated for advanced therapies. So, I think the biggest take away for me is to not lose sight of the long-term goal when addressing short term problems.