Heart Failure Hospitalization - How Bad?

Motivation: Last year I saw an 85 year old man with a stroke.  After never having walked into a hospital or doctor's office, he was in the hospital for diastolic heart failure and was then found to have difficulty moving his left hand.  When talking to him about preventing future strokes and the necessary tests, I wondered whether his heart or his brain was his bigger problem.  What is the prognosis after hospitalization for heart failure?

Paper: Jong, P, Vowinckel, E, Liu, P et. al. "Prognosis and Determinants of Survival in Patients Newly Hospitalized for Heart Failure" Arch Intern Med (2002); 162 (15): 1689-1694.

Methods: Retrospective population-based cohort of 38,702 consecutive patients with first admission for heart failure in Ontario, Canada between 1994 and 1997.  Outcome was mortality at thirty days and at one year.

Results:
Cohort: The cohort of 38702 patients consisted of 51.1% women with 84.6% older than age 65 and 57.9% older than age 75.

Mortality: The net mortality rate was 11.6% at thirty days and 33.1% at one year.  Men had a slightly higher mortality rate at thirty days (OR: 1.09, p = 0.001) and at one year (OR: 1.16, p < 0.001).

Age Relation: Age very significantly affected the prognosis.  The one year mortality rate was 13.5% in those younger than age 50 and 40.1% in those 75 or older.

Comorbidities: Using the Charlson composite index (a composite scale with higher score meaning more number and severity of comorbidities), a patient with score of 0 had one year mortality of 26.8% while a patient with score of 3 or greater had mortality of 50.6%.  Among specific conditions, malignancy, renal disease, dementia, cerebrovascular disease, and previous myocardial infarction all independently and significantly increased one year mortality.

Conclusion: Excepting in those younger than fifty without significant comorbidities, the prognosis of hospitalization for heart failure is quite grim.  I think that a general figure to keep in mind is that roughly a third will be dead after one year.  For someone, with history of stroke, diabetes, and chronic kidney disease (a quite common combination with Charlson score of 3), roughly half will be dead in a year.  I do not think that families or patients are quite aware or counseled adequately of the implications of heart failure.  Of course, this study has some serious limitations as well - most particularly, therapeutics for heart failure have become more standardized with incorporation of beta-blockers, ACE inhibitors, and ischemic heart disease treatment than in the 1990s.  We really need a similar study on a more modern population though I am not sure that the conclusions will be that significantly different.

The anti-nuclear antibody

Motivation: Midway last year, the anti-nuclear antibody (ANA) test started appearing rather useless to me.  The ANA was positive at some titer in just about everyone we tested, and even when it was positive, we discarded it under the mantra of "non-specific."  What is the range of ANA in the "healthy" population?

Paper: Tan, E.M., Feltkamp, T.E.W., Smolen, J.S. et. al. "Range of antinuclear antibodies in "healthy" individuals." Arthritis & Rheumatism (1997); 40: 1601-1611.

Methods:   Fifteen international laboratories experienced in performing the ANA assay were asked to give samples from healthy individuals of different age groups and from patients with systemic lupus erythematosus (SLE), scleroderma, Sjogren's syndrome, rheumatoid arthritis (RA), and soft tissue rheumatism.  Healthy was defined as working individuals between 20-60 years of age without physical or mental disabilities.  Soft tissue rheumatism consisted of patients with non-articular pain.

Results:
Measurement Variability: Among the fifteen laboratories, inter-laboratory coefficient of variation for ANA was: 50.7% for 1:40 dilution, 44.3% for 1:80, 37.9% for 1:160, and 36% for 1:320.  Intra-laboratory variation was about three times lower than the inter-laboratory coefficient of variation.

Normal Individuals: Overall, 46.7% tested negative on ANA.  31.7% tested positive at 1:40 dilution, 13.3% at 1:80 , 5% at 1:160, and 3.3% at 1:320 dilution.

1:160 dilution: At the the 1:160 dilution, the ANA was 95% sensitive for SLE, 86.5% sensitive for scleroderma, 74% sensitive for Sjogren's, 13.5% sensitive for RA, and 7.7% sensitive for soft tissue rheumatism.  Compared to healthy controls, cutoff of 1:160 is 95% specific.

1:320 dilution: At the the 1:320 dilution, the ANA was 86.8% sensitive for SLE, 83.8% sensitive for scleroderma, 71.1% sensitive for Sjogren's, 2.7% sensitive for RA, and 3.8% sensitive for soft tissue rheumatism.  Compared to healthy controls, cutoff of 1:320 is 96.7% specific.

Discussion: A cutoff of 1:160 appears to me a more reasonable value to use to separate possible pathology from variation in healthy individuals with only 5% of healthy population having titers of ANA higher than 1:160.  To me, other surprising findings were how variable ANA is between laboratories and how poorly the ANA performs in detecting rheumatoid arthritis (only 13.5% sensitive for RA) even though it is a immunologic disorder with positive serologic markers.  These figures must, of course, be interpreted with caution because the healthy population was derived from random samples submitted to laboratories.  Aside from individuals having no physical disability, we do not know more specifics which could affect the performance of ANA.  For instance, would a population of young women or older individuals with cancer have different characteristics in the ANA?