Looking for Tall P Waves

Sorry for the delayed post. Internship was a bit busy last week, but I will post more regularly.  Contributions also welcome!


Motivation: "Right is height" - this is a phrase often used to describe the EKG changes caused by right atrial enlargement.  But, late last week, while listening to a lecture on EKG and description of P pulmonale, I wondered just how reliable is this sign.  Or, are there other better signs of RA enlargement? For background, right atrial enlargement is classically characterized on the EKG by "P pulmonale" or P wave height greater than 2.5 mm in lead II.

Paper: Evaluation of Electrocardiographic Criteria for Right Atrial Enlargement by Quantitative Two-Dimensional Echocardiography. Kaplan, J. D. et. al. J Am. Coll. Cardiol. (1994); 23:747-52. http://www.ncbi.nlm.nih.gov/pubmed?term=8113560%20

Methods: EKGs of hospitalized patient with mild to severe right atrial enlargement on echo were randomly selected and compared against EKGs of age and gender matched healthy controls.  There were 100 patients with right atrial enlargement and 25 control patients.  EKG were interpreted independently by two cardiologists using calipers and magnifying glasses.

Results:

Cohorts: Of the patients with right atrial enlargement, 52 were in sinus rhythm, 41 were in atrial fibrillation, 5 were in atrial flutter, and 2 in ectopic atrial rhythm.  All controls were in sinus rhythm.  Right atrial enlargement was most commonly associated with tricuspid regurgitation (30%), pulmonary hypertension (28%), and cardiomyopathy (14%).

EKG criteria:

1. P wave height>2.5 mm in lead II (P pulmonale), sensitivity: 6%, specificity: 100%
2. QRS axis > 90 degrees, sensitivity: 34%, specificity: 100%
3. P wave height>1.5 mm in lead V2, sensitivity: 33%, specificity: 100%
4. P wave height>1.5 mm in lead V1, sensitivity: 17%, specificity: 100%
5. R/S ratio > 1 in lead V1 (without RBBB), sensitivity: 24%, specificity: 100%
6. QRS amplitude <6 mm in lead V1, sensitivity: 33%, specificity: 92%

Discussion: The most interesting result of the paper, I thought, was the finding that P pulmonale is very insensitive finding though quite specific.  In fact, with the same specificity, we can look with better sensitivity at the P wave height in V2 to determine right atrial enlargement.  Another interesting finding was that often the most sensitive findings relate more to right ventricular enlargement (like QRS axis > 90 or R/S ratio >1 in V1).  Surprisingly, the specificity of this finding, was quite high meaning that almost all people with right ventricular hypertrophy have right atrial enlargement.  Thus, RV enlargement is a surrogate marker for RA enlargement.

This paper, however, has some important limitations.  First, there were 25 controls to match against 100 patients.  A few more controls would have been more desirable to capture the full range of normal.  A higher number of controls would likely have driven down the "100%" specificity of some of the findings.  Secondly, of the 100 patients with right atrial enlargement, only 52 were in sinus rhythm.  So, for findings relating to P wave morphology, the number of subjects was limited.  Overall, I think that the main points to take away are that P pulmonale has low sensitivity and RV hypertrophy can be used as a surrogate marker for RA enlargement.

The Nitro Cure

Motivation: In my first week of internship, I have seen more urinary tract infections than just about anything else.  The first treatment response for uncomplicated UTI is a three day course of Bactrim, but what happens when the patient either is allergic to Bactrim or has resistant bacteria? The second choice has been ciprofloxacin.  But, flipping open UpToDate the other day, I read to my surprise that nitrofurantoin is the recommended first line agent after Bactrim.  The issue got even more complicated when the venerable Goodman & Gilman's claimed that nitrofurantoin should be a second line agent.  So, what are the data and recommendations?

Paper: Trestioreanu, Z. et. al. Antimicrobial agents for treating uncomplicated urinary tract infection in women. Cochrane Database Syst. Rev. (2010) 10:CD007182. http://www.ncbi.nlm.nih.gov/pubmed/20927755

Methods: A meta-analysis of randomized trials with the objective of comparing the efficacy and safety of different empiric antibacterial treatments for acute, uncomplicated UTI in healthy women aged 16-65 years.  The primary outcomes were short (2 weeks) and long term (8 weeks) symptomatic cures.

Results:
Fluoroquinolone vs Bactrim: Both fluoroquinolones and Bactrim are equally effective as empiric therapy for UTI  in the short (CI: 0.97-1.03) and long term (CI: 0.94-1.05) .  Overall, there is no difference in adverse effects among the two agents, but patients treated with fluoroquinolones are less likely to develop rash (CI: 0.01-0.43).

Nitrofurantoin vs Bactrim: Both nitrofurantoin and Bactrim are equally effective for UTI treatment in the short (CI: 0.95-1.05) and long term (CI: 0.94-1.09).  Overall, no difference in adverse effects for the two agents, but patients treated with nitrofurantoin were less likely to develop rash (0.04-0.76).

The meta-analysis did not find sufficient studies to compare nitrofurantoin to fluroquinolone head-to-head.  The analysis went on to further describe efficacies of beta-lactams (which are not summarized here).

Discussion: The surprising fact of the matter is that there are generally no differences in efficacy when treating UTI empirically with fluoroquinolone, Bactrim, or nitrofurantoin.  The decision to promote Bactrim stems more from a public health perspective since resistance to fluoroquinolones is increasing.  Decreased prescription of fluoroquinolones would presumably decrease generation of resistant bacteria.  In empiric treatment of uncomplicated UTI, nitrofurantoin is an excellent alternative to Bactrim and less likely to generate the adverse effect of rashes.  Overall, both Bactrim and nitrofurantoin have equivalent severity of side-effects and equivalent efficacy.  Of note, however, this meta-analysis examined uncomplicated UTI in unhospitalized patients, and the data might be different in hospitalized patients with Foley catheters in place!