Welcome to the The Bad Humors. This is the first in a series of unsuccessful articles that you’ll have the privilege of likely not reading. As well as the first article in the Second Amendment Mini-Series: "The Shotgun Approach." I was feeling patriotic. To know more about what spurred on this entire project, feel free to go to the About page. Now that I got that out of the way you can enjoy the following word salad.
With the reboot of Arrested Development’s (AD) fourth season, my wife and I have been re-watching the entire series to rehash our memories. It’s been great and has reinvigorated my repertoire of AD references that I’ll insert into conversions. Such as the Charlie Brown feeling I used to get my intern year on OB when a triage patient would decline a male provider. However, this also has had unintended consequences. Specifically, Amanda’s hatred of the “British Eyes Only” audio clip that played throughout the third season. Unfounded disdain but somehow understandable. I tend to agree with her as I also get a familiar sense of unexplainable annoyance when I hear it as well. And it is the best way I can explain my relationship with BNP.
BNP - Brain Natriuretic Peptide – first started gaining notoriety in the late 1980’s/early 1990’s alongside it’s now rather defunct cousin Atrial Natriuretic Peptide (ANP). Both are thought to be equally important in counteracting the RAAS and sympathetic activity, effectively limiting sodium retention and vasoconstriction in heart failure. Its use is preferred over ANP as it has a larger range of variability and is thus able to pick up smaller changes. I like to think of BNP like the Dark Knight - the lab that heart failure deserves, but not the one it needs right now. The “right now” part is the thing I have the most beef with, as it is all too convenient get it “right now” as well as trend it. Here are the 3 uses of BNP I’ll be evaluating with extreme prejudice.
Question 1: Let’s start with the first one since it’s the use I hate the most, BNP trending. It really makes me cringe in the hospital when I hear anyone say “the BNP is 'blank' trending thus…”. I honestly don’t care what is said after the “thus” and typically will judge someone silently. I’m a big fan of the clinical exam when it comes to a lot of things and progression of heart failure (HF) is definitely one of them. But what does the evidence say? Well, I’m happy to report the evidence shows no difference in every meaningful clinical outcome (30 day mortality, in-hospital mortality, 30 day readmission, and mean length of stay) with trending BNPs vs monitoring clinically.  We have the REDHOT II (N=447) trial to thank for that which is really the only RCT that has evaluated BNP trending for acute HF . Until something else comes along to prove otherwise, that’s enough evidence for me to continue to hate on serial BNP trending in the hospital.
But being a Family Physician, I would be remiss if I didn’t address the use of BNP in the outpatient setting. This is something I have personally never done and looking at the evidence opened my eyes a bit on its effectiveness in that setting. There is great, level 1 evidence showing mortality benefit with the use of BNP-guided treatment in HF. This primarily comes from a meta-analysis of 8 RCTs in 2010 which found the risk of all-cause mortality was significantly lower in the BNP-guided group (RR 0.76, 95% CI, 0.63-0.91) but no difference in all-cause hospitalization and mortality benefit in a subgroup analysis of patients older than 75 years.  There’s one caveat though in that the BNP-guided groups were found to have more ACE-I and beta-blocker treatment (21/22% vs. 11/12%). Hey, that’s still pretty good. I think I’ll start considering BNP as outpatient guidance in my patient’s younger than 75 years.
Question 2: Building on the momentum of my new BFF REDHOT, let’s look at the evidence regarding the use of BNP for the actual diagnosis of HF. In my vast experience of 14 months of MD'dom, I’d say clinicians are typically better about using the BNP properly in this scenario. That is, using it to rule OUT HF but not to rule IN HF. And they’re right. There are Mounds of evidence in supporting the good sensitivity and poor specificity of the test. Renal failure, valvular and coronary heart disease, pulmonary hypertension and sepsis can all elevate BNP. One systematic review from 1989-2005 found pooled sensitivity of 92% and specificity of 65% for diagnosis of heart failure.  A different systematic review also in 2006 found a bit more scattered results but with general same trend with sensitivities ranging from 20-100% (Seriously? Overall most studies were >80%) and specificities ranging from 47-89%. There were several others before these studies that corroborated the number crunching as well . So takeaway from this is that you can continue to be confident in BNPs (standard is usually < 100 pg/ml) when ruling out HF. Just don’t diagnose heart failure with it.
Question 3: For the three of you that are still with me (hi Mom), let’s polish off this last question: How useful is BNP in differentiating HF from other causes of acute dyspnea? The answer lies in the masterfully titled “Breathing Not Properly” study in 2002 (N=1586) . This is probably the most cited and famous of the BNP studies. It was conducted in ED and urgent care settings where they looked to distinguish between HF and pulmonary causes of dyspnea in the acute setting.
What they ended up finding in the study was a pile of obvious. So obvious, one may even… Snicker at it (had to). Plasma BNP was markedly higher in patients with clinically diagnosed HF than those without (675 vs. 110 pg/mml). Sensitivity, specificity, and predictive accuracy were on par with other studies (90, 76, and 83%). While choosing higher values such as >125 and >150 pg/ml decreased sensitivity, increased specificity, and did not change overall predictive accuracy.  They also compared it to other modalities (CXR, history of HF, and rales on exam) and were found to be equivalent to or better. The most interesting finding from the study was the death-match between plasma BNP vs. clinical judgment. No surprise here as BNP was more sensitive (90 vs. 49%) but less specific (73 vs. 96%) than clinical judgment. The lessons learned for me here is that again, <100 pg/ml works for me when ruling out HF. Also, if I was stuck in the very common conundrum of “is this a COPD or a CHF exacerbation?” then I would need a rather high BNP to push me into the CHF camp. For my own clinical practice, I will probably use the 675 pg/ml average they found as my bar.
So what did I learn from all this? There is an overwhelming amount of literature on BNP. What I wrote was only the tip of the iceberg with only what I believe to be the very most relevant data to answer my questions. I also learned that I can rest assured that I can continue to ridicule many of the in-hospital BNP use for the above reasons but at the same time incorporate BNP into my outpatient practice. Finally, writing this reminded me that I need to quit writing this and finish the 3rd season of Arrested Development again.
Feel free to blast me in the comments.
TL; DR - Don't trend BNP inpatient but can consider doing it as an outpatient. Stop using it to diagnose heart failure if you were doing it before.