CME-MOC Credit

Time Stamps

  • 03:39 Sodium restriction guidelines
  • 07:20 Current data in outpatient data
  • 11:35 Do inpatient studies show signal?
  • 13:52 Physiology behind sodium balance
  • 16:37 Take away and clinical applicability  

Show Notes

  • Major cardiology organization guidelines recommend salt restriction to improve outcomes in heart failure.
    • However, the strength of these recommendations have been gradually downgraded in progressive editions.
  • While data for improved clinical endpoints with hypertension is robust, the data for heart failure is limited.
  • Some outpatient randomized controlled trials, while plagued with biases and confounders, have even signaled potential harm.
  • Outpatient data studies rely on patient reported assessments of their salt intake, which can be very tricky.
    • GOURMET-HF, was a trial designed to combat this, which randomized patients to receive low salt pre-prepared meals.
    • While it showed a trend towards decreased re-admissions (11 vs 27%), it was not statistically significant.
  • While the inpatient environment can ideally be used to control all the variables, the data does not show any difference. 
    • There are a few small trials randomizing inpatients to salt restricted diets or usual care, with no clinical improvement for those on restricted diets.
  • There is some thought that since salt restriction will decrease sodium delivery to the kidneys, this may lead to upregulation of the neuro-hormonal systems that evidence-based medical therapy seeks to block.
    • The large prospective study noted above did show worse outcomes with salt restriction, however the adverse effects seemed to be limited to those not on ACEI/ARB.
    • This suggests that patients who cannot tolerate ACEI/ARB may be particularly at risk for adverse outcomes of salt restriction, possibly due to the above proposed mechanism.
  • There is an upcoming trial called SODIUM-HF that hopes to address this issue with better quality data. 

Transcript

AN: Today we’d like to delve into an issue many of you may consider so obviously true, so set in the medical dogma, that you might not even know it’s controversial

J: Are we going to encourage smoking?

S: Or maybe give antibiotics for URIs?

AG: Haha, ok not that set in the dogma. But another topic, near and dear to my, and many of our patient’s hearts. 

…. [crickets]

AG: I would say this isn’t a discussion for the faint of heart, but it is exactly that.

AN: Aaaand, the first of many bad puns from Armand. 

J: Who can resist? But yes, we are going to be talking about big bad heart failure today

AG: How many times has “dietary indiscretion” been blamed for a hospital admission for a heart failure exacerbation?

AN: Pretty much every admission.. but why exactly do we tell them to avoid salt?

J: Uhhh, I thought it just sort of made sense, right?

S: Yeah, salt leads to  fluid retention, and then we need to give them diuretics to get volume off, so OBVIOUSLY it’s good for patients with heart failure to eat less salt in the first place.

AG: What if we told you – everything you’ve learned about salt in heart failure is a lie.

J: Everything?

AG: Everything.

AN: Okay, maybe not everything. Armand’s prone to sensationalism. But, in reviewing the data on sodium restriction, you may be surprised to find that not only can salt restriction be ineffective, but it may even be HARMFUL for some patients.

S/J: GASP!

AN: Totally crazy, right?

J: Is this coming from the same people who decided Pluto wasn’t a planet?

S: Well I just learned that the moon is not the only moon we have…

AG: That’s no moon …it’s a space station.

INTRODUCTIONS

J: Hi I’m Janine Knudsen

S: and I’m Steve Liu

J: Welcome to Mind the Gap… We’d like to thank Dr. Mahek Shah, advanced heart failure attending at Thomas Jefferson University Hospital for peer reviewing this episode. Check out his podcast Heart Success for insights and updates in the world of cardiology.

S: We also have 2 exciting guests today –

AN: Hi, I’m Abhinav from Jefferson.

AG: And I’m Armand from the University of Miami.  

S: Now for listeners who haven’t heard of The Scope, it’s a really cool publication

J: Yes! I love the Scope – it’s a free weekly email I’ve been following since med school. It’s great because it helps me stay on top of the most relevant internal medicine literature, but it’s short and usually pretty funny!

AG: Thanks for reading Janine – we have a lot of fun with it. You can sign up at www.MedicineScope.com, and follow us on Twitter @MedicineScope

J: We’re so excited to have Armand and Abhinav here today to talk about this important and surprisingly controversial topic.

S: Alright guys, take it away

AG: This is how we’re going to do it: first, we’ll review the current guidelines around sodium restriction

AN: Then we’ll review the available data from randomized trials on sodium restriction to see what the data really says

AG: After that I’d like to poke the hornets’ nest just a little, and show that the physiology we thought was at play may not be as straight-forward as we’ve been led to believe

AN: Yikes. Hornets. And finally we’ll do our best to synthesize this information and reflect on how best to apply this to our patients.

GUIDELINES – PART 1

J: So Abhinav, to get started, what do the major guidelines say about salt restriction?

AN: So, first off it’s important to know that all major cardiology guidelines recommend salt restriction to improve outcomes in heart failure.  

AG: That’s the AHA/ACC, the ADA (diabetes!), the ESoC (european society of cards), and EVEN the Australians.

AN: However, it should be noted that the strength of these recommendations have been sneakily and gradually downgraded in progressive editions.

AG: Very Sneakily. The 2009 ACC/AHA guidelines gave sodium restriction a Class I recommendation for patients with symptomatic heart failure, despite having only Level C Evidence, meaning limited data and only expert consensus.  

AN: Just as a reminder, there are 3 levels of evidence. The best – Level A evidence – requires multiple RCTs and/or a meta-analysis

AG: But in 2013, they downgraded this to a Class IIa – or “moderate” –  recommendation, stating that sodium restriction is “reasonable” in those with symptomatic HF to reduce congestive symptoms. 

And if you dig into their section “Evidence GAPS and Future Research Directions” snuck in the middle there is this quote: “Even the widely embraced dictum of sodium restriction in HF is not well supported by current evidence.”

J: What??!?! They just dropped that in there like it’s no big deal? 

AG: Yup, and buried along with that stunner is another unexpected recommendation. They stratified recommendations based on the clinical stage of heart failure, in a way that may seem counterintuitive.

S: How’s that, Armand?

AG: Well for NYHA Class I-II patients, they suggested <1.5g daily sodium intake, but for Class III-IV patients, more symptomatic patients, they suggested a higher cut off: less than 3.0g of intake.

S: So what you’re saying is that they let patients with worse HF eat more salt? That’s a bit strange — 

AG: Weird right? It’s hard to know whether this reflects an inconsistency on the part of policy-makers or a response to some of the conflicting data that exists on the subject. There’s actually some data suggesting POORER outcomes with excessive sodium restriction in those with more severe heart failure.

J: Oooh I think you’re referring to my favorite concept: the J curve! 

S: You’re a little biased, Janine, save that for later! 

AN: Don’t worry, we’ll get to it Janine. So about salt restriction in general, the European guidelines don’t help us out much either. They only recommend “avoiding excess salt intake…”   Basically the generic, blanket recommendation I’ve been giving my patients on the subject since residency.

J: Ok, but why all this backpedalling in recent years? 

AN: Well, guidelines have always been very clear in recommending salt restriction to avoid developing heart failure in the first place. 

AG: I think this is a key point and probably where the big emphasis on “salt is bad” came from. Numerous studies have demonstrated a strong relationship between salt and hypertension, which is one of the biggest modifiable risk factors for developing heart failure. 

AN: And to prevent or reduce HTN, current US guidelines for HTN suggest 1.5 – 2g of daily sodium intake

AG: which may not seem like a lot, but the average American consumes about 3.4 – 3.7g per day.

S: Ok, so what you’re saying is there’s robust data to support a low salt diet for hypertension, and hypertension can lead to heart failure, but somehow that doesn’t mean low salt is actually good for heart failure?

AG: Exactly, it’s not that linear.  The data for salt restriction in patients who already have heart failure may not be as cut-and-dry as we think.

J: Duh Duh Duhhhh 

DATA – PART 2

AN: Okay, so the first thing to know about the literature around salt restriction in heart failure, is that a good number of the RCTs were conducted by an Italian group, with many of the same investigators including Licata, Paterna, and Parinnello.  

AG: Now, they’ve done a lot of research on this subject, examining various strategies, including fluid restriction, sodium restriction, and various diuretic dosing schemes.  

AN: It’s a little hard to draw obvious practice-changing conclusions from their results because they studied many of these strategies simultaneously, and instead of primarily clinical outcomes, most of their studies focused on physiologic biomarkers and lab values like BUN or serum creatinine. 

AG: Yes, they didn’t have the cleanest study design. But one thing definitely worth mentioning from their studies is that adverse events were surprisingly MORE COMMON in patients who were prescribed a low-salt diet. 

J: The J curve!

AN: Yes, exactly!  They saw that the lowest salt intake (<2g daily) was actually associated with increased mortality and hospital admissions.  

J: But can we trust the data?

AN: Maybe, if we understand the pitfalls: 1) that it was very difficult to measure patient’s true sodium intake, 2) that important potential confounders like fluid restriction were not controlled, and 3) that many of these patients were not on optimal guideline-directed medical therapy. 

AG: Ok, that may be too messy for me. But it’s hard to completely ignore these findings since they’ve been replicated in other studies. 

AN: Yeah, in 2016, a Chicago group published the HART study (Heart Failure Adherence and Retention Trial): a prospective, propensity matched study looking at data from over 900 patients with class II and III heart failure. They surveyed patients about their salt intake, and then stratified them into low-salt (<2g) or moderate-high salt groups. Ultimately, 300 patients of the 900 were propensity-matched.  And here the results were dramatic. Death or HF hospitalization was much higher in the low-salt patients, 42 vs 26%. 

S: Woah, consider me impressed. But I’ll still nitpick and say this isn’t an RCT, it’s a propensity matched cohort-study, and I’m not sure food frequency questionnaires are super reliable in measuring salt intake.  

J: And can I just ask: how feasible it is for patients to actually even accomplish adherence to a low-salt diet given how salt is in processed food nowadays? 

S: Delicious salt everywhere! It is the best of times, it is the worst of times.

AG: Great points guys.  You’re not alone — others have had the same concerns. A more recent study, GOURMET-HF tried to tackle this issue by providing home-delivered meals to patients post-discharge for heart failure exacerbations. 

S: Sign me up! 

AG: Sorry Steve, only patients with heart failure, and it was a pretty small trial: Sixty-one patients were randomized at hospital discharge to receive 4wks of low salt (<1.5g) DASH-compliant meals vs usual care. 

J: So they knew exactly what their patients were eating.

AN: Exactly, or at least as close to it as we may be able to get.  The primary outcome was quality of life, but investigators also looked at clinical markers and adverse events like hypotension, renal function, and hospital readmissions.

J: So what did this cleverly named GOURMET study show? 

AN: Well, there were no changes in QOL scores between the groups, and no statistically significant difference in clinical outcomes.

S: Nooooooo! What a waste of a name!!!!

AG: Well if it makes you feel any better,  this was a small trial, and there was a TREND towards significance for improved clinical status and a decreased rate of hospital readmissions in the low-salt group (11 vs 27%).

J: Ok, so pretty good even if it’s not a slam dunk for salt restriction! 

AG: Perhaps some good news, but just remember that even the best diet studies are at risk for bias, like unclear adherence and potential confounders.

S: Yeah, outpatient dietary studies are notoriously hard. There’s just so much variability when patients are out and about. 

J: What if there was a way to keep people confined in one place, watch their every move, regulate everything they eat, and monitor them constantly?

AG: That’s called jail Janine…

AN: Haha, I’ll confess I’ve had more than one patient admit to me that he felt imprisoned in the hospital.  But I hear what you’re saying Janine. Do we have any data from inpatients? Does sodium restriction in the hospital for patients with heart failure make any difference?

J: It MUST, right?

Long pause…

S: Say it ain’t so…

AG: Sadly…

S: How?! We put everyone on low-salt diets!

AG: And yet, the data isn’t very robust. Are you surprised? This is the theme of the day. You invited us on to burst bubbles.

AN: Haha we come in peace, and in the name of education and a more global understanding! Okay, so, in 2013 a Brazilian group looked at 75 inpatients with acute decompensated heart failure. 

AG: Patients were randomized to a salt and fluid restricted arm (a cold-blooded 800cc fluid and 800mg of salt), or an unrestricted arm. 

AN: The primary end-point was weight loss and clinical stability at 3 days. And the study showed NO difference between the groups by the trial’s end.

AG: They also found no significant differences in the median length of stay, use of IV diuretics or vasodilators/inotropes, lab data, or 30 day readmissions.   

AN: Can you guess what the only significant difference was between the groups?

S: Irritability.

AG: Close! The only difference they found between the groups was that the restricted patients reported more thirst. 

AN: And probably irritability.

AG: And probably definitely irritability.

AN: It’s worth noting that they didn’t clearly specify rates and dosages of various medications. This is important, I’d be curious to see if beta-blockers, or ACEi’s were different between groups or had any sort of interaction with the outcome.

AG: And again, like some of the Italian studies we mentioned earlier, this data is a little muddled — we’re not just looking at sodium restriction – they threw in fluid restriction at the same time.

S: But the takeaway is that even in this randomized control trial in the hospital, where we can control nearly every detail, we still don’t see any meaningful clinical improvement with salt restriction.

AG: Sadly no Steve

S: Well Pluto is still a planet in my book – you can’t take that one away from me

MECHANISMS – PART 3

AG: Okay, let’s try to make sense of all of this. How could sodium restriction actually make things worse? Cardiology isn’t all that complicated. 

AN: So easy, even a cardiologist can do it!

J: So here’s my thinking: More salt = more fluid retention = volume overload = badness. So, shouldn’t it follow that less salt = less fluid retention = better volume status = goodness?

AG: Maybe it’s not so simple. Remember that most of our guideline-directed therapies for heart failure aim to block the neurohormonal signaling of the renin-angiotensin-aldosterone system (also called RAAS). 

J: Ok right, ACE-inhibitors and ARBs tone down angiotensin and aldosterone to relax the vasculature and promote diuresis.

AN: Right. To oversimplify a little bit: The kidneys secrete renin in response to perceived hypovolemia either from decreased perfusion or low salt delivery to the kidney

AG: Renin it’s the R in RAAS!

AN: Renin then cleaves angiotensinogen to angiotensin I. 

J: Right Angiotensin is the first A in RAAS

AN: This is converted by ACE to Angiotensin II, which has numerous effects including direct vasoconstriction, tubular sodium reabsorption, ADH secretion (which causes H2O reabsorption), and aldosterone secretion from the adrenals  

S: Ah aldosterone, the second A!

AN: Correct, aldosterone, which also causes sodium reabsorption.AG: It’s important to remember that patients with heart failure  may already have low circulating blood volume, and their nephrons may respond differently than their healthy counterparts.

AN: So while decreasing salt intake may initially cause less fluid retention, it may actually increase RAAS activation and paradoxically have the opposite effect. 

S: Ok, I think I’m following, salt restriction may make them functionally volume-depleted,  and then might crank up the neurohormonal system that we’re trying to dampen.

AG: Exactly. And this may be especially true in patients who are not on appropriate neuro-hormonal blockade. Now if you remember back to the HART study — patients in the low-salt group had worse clinical outcomes than their liberalized sodium counterparts. 

AN: Yep, but when you looked into that low-salt group, the worse outcomes were in patients not on ACE-I/ARBs. Patients that were on these meds were actually spared from having worse heart failure outcomes. 

J: Interesting, so salt restriction may be especially bad if we aren’t blocking your body’s homeostatic counter-measures like the renin-angiotensin-aldosterone system. 

AG: Yes! At least that’s the physiological explanation Cardiologists have come up with to explain what the data shows. Just remember, we’re trying to connect the dots with imperfect data — all of these trials have their limitations. 

SYNTHESIS – PART 4

S: Ok so now that our world has been blown, let’s try to put together everything that we talked abou

AN: Sure. So, while all major cardiology organizations still recommend salt restriction for patients with heart failure, they admit the quality of the evidence is weak at best, and they have been steadily downgrading the strength of these recommendations in recent years.

AG: The existing data is sparse, and the little data that we do have from randomized trials hasn’t been all positive. There may even be a signal of harm for select patient populations from the larger outpatient studies, but these studies have been observational and subject to bias.

J: And I like the physiology that we just broke down, it sounds like salt-handling in patients with heart failure is complicated.

AN: See you acting like it’s somebody else gets me frustrated! (keeps singing)

AG: It’s complicated and there is the potential for patients without sufficient neurohormonal blockade to perhaps do worse with salt restriction.

S: So how do you put this together for how to treat real patients?

AN: Salt restriction is still recommended in the guidelines for patients with heart failure, but remember it is a MODERATE recommendation with weak evidence. 

AG: Yes I think keeping in mind the strength of recommendations and the quality of evidence is always important. Your decisions will have to be made on an individualized patient-to-patient basis. 

AN: Probably more important than anything else is ensuring that they’re on (and they’re taking) the right meds, and uptitrating these as much as you can. There’s a lot of data out there showing that we really do a much poorer job than we’d like to think at increasing the dosages of heart failure meds  to reach target milestones — but that’s a subject for another day.

AG: But that said, it’s probably not necessary to come down on your patients too harshly for sneaking some extra seasoning onto their food.

S: I feel like everyone is always blaming dietary indiscretion when we can’t diurese them in the hospital. Some apologies are probably in order. 

J: Yeah, for sure Steve.

AG: It’s really hard to say if it makes a difference, and the evidence just isn’t there. Being kind and not blaming patients is certainly always a winner though. 

AN: An upcoming trial to be aware of that investigates this topic further is the Candian-led SODIUM-HF.  This is a multicenter, multinational trial of patients with chronic heart failure who will be randomized to low-salt (<1.5g) and usual care arms. They are currently still enrolling patients, so it’s unclear when results will be available. 

AG: Will this help clarify the issue? We’ll see…

References

 

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