ment was 17.5%. Each patient was fol-
lowed for Ն12 months. None of the
patients received prophylactic ICDs in
the first year of enrollment. Nonethe-
less, 40 of 41 were alive at 1 year,
corresponding to an extremely low
1-year mortality rate of 2.44%. This
was not an outlier, because in a similar
survey 10 years ago, the 1-year mortal-
ity without ICDs of 27 newly enrolled
patients with a mean LVEF of 18.3%
was 0%. In contrast, the usual 1-year
mortality of patients after heart failure
hospitalizations ranges from 20% to
30%.
3,4
The only patient in our 2010
cohort who died within 1 year was a
woman with end-stage DC and an
LVEF of 5%, who was not a candidate
for advanced treatments because of my-
eloma, was receiving home milrinone
infusion, and was under hospice care.
Twenty-five of the 41 patients under-
went repeat echocardiography at 1 year
after enrollment. In those, the mean
LVEF increased from 18.8% before en-
rollment to 36.3% at 1 year (absolute
mean increase 17.5%, relative increase
93.1%). Fifty-two percent of patients
achieved LVEFs Ͼ35%, which is out-
side the SCD-HeFT ICD indication
range.
2
The study by Zecchin et al
1
clearly
demonstrated that with optimum medi-
cal management, many patients with
original SCD-HeFT criteria for prophy-
lactic ICD implantation did not main-
tain ICD indication at 3 to 9 months into
treatment. Our data extend those obser-
vations by demonstrating that with ag-
gressive medical management, even
high-risk patients with severe symp-
toms and very low LVEFs at presenta-
tion can do well, have very low 1-year
mortality, and have great improvement
in the LVEF, in many cases moving
them outside the ICD indication range.
There is considerable debate about
the optimum timing of prophylactic
ICD placement in patients with non-
ischemic DC.
1,5–7
Our data suggest that
for patients who are followed by an
intensive disease management program,
it may be prudent to pursue aggressive
medical management without prophy-
lactic ICD implantation for Ն1 year af-
ter a recent diagnosis of DC. Such a
conservative approach, however, man-
dates site-specific continuous quality
control and repeat assessment of the
1-year risk for sudden death of all pa-
tients who were not treated with ICDs.
Laszlo Littmann, MD
Sara Y. Narveson, NP-C
Nicole M. Fesel, RN
Sarah L. Marconi, PharmD
Charlotte, North Carolina
4 April 2012
1. Zecchin M, Merlo M, Pivetta A, Barbati G,
Lutman C, Gregori D, Serdoz LV, Bardari S,
Magnani S, Di Lenarda A, Proclemer A, Sin-
agra G. How can optimization of medical treat-
ment avoid unnecessary implantable cardio-
verter-defibrillator implantations in patients
with idiopathic dilated cardiomyopathy pre-
senting with “SCD-HeFT criteria?” Am J Car-
diol 2012;109:729 –735.
2. Bardy GH, Lee KL, Mark DB, Poole JE,
Packer DL, Boineau R, Domanski M, Trout-
man C, Anderson J, Johnson G, McNulty SE,
Clapp-Channing N, Davidson-Ray LD, Fraulo
ES, Fishbein DP, Luceri RM, Ip JH; Sudden
Cardiac Death in Heart Failure Trial (SCD-
HeFT) Investigators. Amiodarone or an im-
plantable cardioverter-defibrillator for con-
gestive heart failure. N Engl J Med 2005;
352:225–237M.
3. Siirilä-Waris K, Lassus J, Melin J, Peuhkuri-
nen K, Nieminen MS, Harjola VP, for the
FINN-AKVA Study Group. Characteristics,
outcomes, and predictors of 1-year mortality in
patients hospitalized for acute heart failure.
Eur Heart J 2006;27:3011–3017.
4. Chen J, Normand SLT, Wang Y, Krumholz
HM. National and regional trends in heart
failure hospitalization and mortality rates for
Medicare beneficiaries 1998-2008. JAMA
2011;306:1669 –1678.
5. Bänsch D, Antz M, Boczor S, Volkmer M,
Tebbenjohanns J, Seidl K, Block M, Gietzen
F, Berger J, Kuck KH, for the CAT Investiga-
tors. Primary prevention of sudden cardiac
death in idiopathic dilated cardiomyopathy:
the Cardiomyopathy Trial (CAT). Circulation
2002;105:1453–1458.
6. Kadish A, Schaechter A, Subacius H, That-
tassery E, Sanders W, Anderson KP, Dyer A,
Goldberger J, Levine J. Patients with recently
diagnosed nonischemic cardiomyopathy bene-
fit from implantable cardioverter-defibrillators.
J Am Coll Cardiol 2006;47:2477–2482.
7. Verma A, Wulffhart Z, Lakkireddy D, Khay-
kin Y, Kaplan A, Sarak B, Biria M, Pillarisetti
J, Bhat P, Di Biase L, Constantini O, Quan K,
Natale A. Incidence of left ventricular function
improvement after primary prevention ICD
implantation for non-ischemic dilated cardio-
myopathy: a multicenter experience. Heart
2010;96:510 –515.
http://dx.doi.org/10.1016/j.amjcard.2012.04.008
Findings of a Relation Between
Vitamin D and C-Reactive Protein:
Concerns About Methods Used and
Conclusions Drawn
The epidemiologic study suggesting
a relation between serum 25-hydroxyvi-
tamin D (25[OH]D) and C-reactive
protein (CRP) by Amer and Qayyum
1
is timely, given the prominence of
25(OH)D in recent scientific research
and the recent increase in vitamin D
recommended daily allowances.
2
How-
ever, the study appears to suffer from
deficiencies in internal validity (due to
the analysis methods used) and external
validity (because vitamin D supplemen-
tation by subjects was not included in
the analysis). Their findings contradict
evidence for a dose-dependent reduc-
tion of coronary heart disease mortality
with higher serum 25(OH)D,
3
and fur-
thermore, CRP has questionable utility
in guiding treatment of patients with
coronary heart disease.
4
Best practices
in data analysis suggest several steps
that should have been taken to avoid
bias and uncertainty.
The scale of the y axis in Figure 1
should have been back-transformed
from the logarithm of CRP to its raw
(original) value. The investigators’ mul-
tivariate analysis results are counterin-
tuitive, because in Table 1, we can read
that subjects with 25(OH)D levels Ͻ21
ng/ml had higher mean CRP levels
than subjects with 25(OH)D levels Ͼ21
ng/ml. An appropriately scaled graph
would allow readers to visually grasp
the relations being examined and assess
the conclusions being drawn: is it
graphically obvious that CRP increases
at serum 25(OH)D levels Ͼ21 ng/ml?
When building a statistical model,
one can introduce bias into the model
5,6
or, even worse, mathematically create
associations that are not there in real
life (e.g., by including variables such
as coronary heart disease, which may
be on the causal pathway between
25[OH]D and CRP). The investigators
provided considerable generic details of
how variables were measured in the Na-
tional Health and Nutrition Examina-
tion Survey (NHANES) but did not jus-
tify their choice of including those
variables in multivariate analysis. A
structured approach to statistical mo-
del building with an a priori rationale,
guided by modern understanding of
causality
7
and model-fitting tools such
as the Akaike criterion, can help avoid
or reduce these biases.
8
It is thus possi-
ble that on reaching steps 5 to 9 of their
stepwise model-building process (Table
2), the investigators may have achieved
a model that yielded significant

co-
efficients but was in fact a poorly fit-
ted model.
162 The American Journal of Cardiology (www.ajconline.org)