Baylor University Medical Center Proceedings April 2017 - 140

Table 2. Drug classes and dosage used to calculate
therapeutic intensity index
Oral dose
Drug or equivalent

Low = 1 Moderate = 2 High = 3

Enalapril (mg bid)

<10

10-19

≥20

Valsartan (mg bid)

<80

180-159

≥160

Carvedilol (mg bid)

<12.5

12.5-24.9

≥25

Spironolactone (mg qd)

<12.5

12.5-24.9

≥25

<30

30-59

≥60

Isosorbide mononitrate (mg qd)

<25

25-49

≥50

<0.125

0.125-0.24

≥0.25

<20

20-79

≥80

Hydralazine (mg qid)
Digoxin (mg qd)
Furosemide (mg bid)

bid indicates 2 times/day; qd, daily; qid, 4 times a day.

transformation corrects the observed right-skew of the MISS
distribution, which is constructed from biomarkers bounded
by zero, but potentially having relatively large values. A biomarker having the same value after a patient receives treatment
as before the patient receives treatment has a ratio of 1 and a
log score of 0. Further, biomarkers changing by a scaled factor
of 10 have log10 values between -1 and +1, which is appealing.
For the baseline visit, the MISS score was calculated using the
upper limit of normal of the corresponding biomarker as the
denominator.

Based on the pharmacologic regimen of the HF drugs, a
therapeutic intensity index was formulated for each patient after
every visit. The index was based on HF drug classes and their
corresponding doses, which ranged in intensity from 1 to 3.
The summed therapeutic intensity index ranges from 0 to 24,
with 24 being the highest intensity of medical management.
Table 2 provides the details of the drugs and their corresponding
intensity scores.
RESULTS
Four of the 8 patients were randomized to the biomarkerguided management (B) arm, and the remaining 4 were randomized to the usual clinical management (UC) arm. The
median age of patients was 57.5 years (range 52-71) in the B
arm and 56 years (range 43-65) in the UC arm. There were 5
men (3 in B and 2 in UC) and 3 women (1 in B and 2 in UC).
The etiology of HF was considered ischemic in 6 of the patients
included in this study (3 each in the B and UC arms). Three of
the 4 patients randomized to the B arm had diabetes, while only
one patient in the UC arm had diabetes. All patients included in
this case series had hypertension, and 2 and 3 patients in the B
and UC arms had dyslipidemia, respectively. The demographic
details and comorbidities are shown in Table 3.
Table 4 shows the therapeutic management and MISS for
each of the 8 patients. Figure 1 shows the baseline MISS segregated by age, and Figures 2 and 3 show the changes in the
MISS and therapeutic intensity index for each patient. For patients on biomarker-guided management, the pharmacologic

Table 3. Patient demographics and clinical characteristics
Biomarker-blinded management
(usual clinical management, UC)

Biomarker-guided management (B)
B1

Variable
Age (years)
Gender
Race
(kg/m2)

UC1

UC2

UC3

UC4

Male

Female

Male

Female

Male

Female

Male

Black

White

Black

White

Black

20.5

30.8

34.6

39.7

16.9

34.2

25.8

40.4

Nonischemic

Ischemic

Nonischemic

Ischemic

New York Heart Association functional class

III

Diabetes mellitus

Hypertension

Dyslipidemia

Peripheral arterial disease

Body mass index

Cause of heart failure

Prior myocardial infarction

Cerebrovascular accident

Smoker

Atrial fibrillation

Prior percutaneous intervention

Prior coronary bypass

Implantable cardioverter defibrillator

0 indicates No; +, Yes.

140

Baylor University Medical Center Proceedings

Volume 30, Number 2

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