Baylor University Medical Center Proceedings April 2017 - 139

Personalized treatment of heart failure with biomarker
guidance using a novel disease severity score
Anupama Vasudevan, BDS, MPH, PhD, Hourossadat Hashemi Jazi, MD, Jane I. Won, BS, Timothy Ball, MD,
Gautam R. Patankar, MD, Syed A. Sarmast, MD, Hyun Joon Shin, MD, and Peter A. McCullough, MD, MPH

We propose a novel Myocardial Injury Summary Score (MISS) integrating
the 4 biomarkers suggested by the 2013 American College of Cardiology/
American Heart Association guidelines for management of heart failure.
In this case series, we examined 4 heart failure patients who received
treatment guided by the biomarker results and 4 patients who received
routine clinical management with no information about the biomarkers. Most of the patients receiving biomarker-guided management had
medications adjusted based on the biomarker values, while no changes
were recommended for patients in the biomarker-blinded category. This
case series suggests that biomarker-guided therapy with serial biomarker
values leads to timely therapeutic adjustment and that biomarker values
as a composite score can be used effectively to measure the severity
of heart failure.

A

bout 5.7 million Americans suffer from heart failure
(HF) (1), and the mortality rate is approximately 50%
over 5 years for a patient newly diagnosed with HF
(2). The prevalence of HF has been documented to be
increasing, given prolonged survival due to better treatment
modalities (3). Cardiac biomarkers have been recommended
as prognostic and diagnostic tools in the clinical management
of HF, and American College of Cardiology/American Heart
Association guidelines have suggested the use of 4 biomarkers-
B-type natriuretic peptide (BNP), troponin, galectin-3, and
suppression of tumorigenicity 2 (ST2)-to guide the prognosis of patients with HF (4). Management of HF with routine
biomarkers as part of the follow-up was shown to increase the
survival benefit for these patients (5). We incorporated the 4
recommended biomarkers into the Myocardial Injury Summary
Score (MISS) (6), a novel score to measure the severity of HF. In
this case series, we examined 8 HF patients who received either
treatment guided by the biomarker results or routine clinical
management with no information about the biomarkers. This
study was approved by the Baylor institutional review board
and funded by the Cardiovascular Research Review Committee.
METHODS
HF patients who were ambulatory with an ejection fraction
<40% and an estimated glomerular filtration rate ≥30 mL/
min/1.73 m2 were included in this study. The patients were
Proc (Bayl Univ Med Cent) 2017;30(2):139-142

Table 1. Drug titration chart for biomarker-guided therapy
Marker result

Protocol-directed drug titration step

Troponin I >99% detection
limit

Add or up-titrate isosorbide mono- or dinitrate
every month to maximally tolerated

B-type natriuretic peptide
>100 pg/mL

Add or up-titrate furosemide every month to
maximally tolerated

Galectin-3 >25.9 ng/mL

Add or up-titrate enalapril or valsartan or
spironolactone every month to maximally
tolerated

Suppression of
Add or up-titrate carvedilol or long-acting
tumorigenicity 2 >35 ng/mL metoprolol every month to maximally tolerated

randomized to either management based on the biomarkers
obtained at each visit or by standard clinical management, where
the clinicians were blinded to the results of the biomarkers. The
advocated therapeutic management for the biomarker-guided
therapy is detailed in Table 1.
For each patient, the 4 biomarker values were integrated into
a novel score to measure the severity of HF. The basic metric is
the ratio of the biomarker value at the current office visit to the
baseline value obtained during the previous office visit:
Biomarker(i)Current visit

∑i log10 Biomarker(i)
Prior visit
MISS =
n

where n denotes the number of total available biomarkers and
i denotes BNP, troponin, galectin-3, or ST2. The logarithmic
From Baylor Heart and Vascular Institute, Dallas, Texas (Vasudevan, Won);
Texas A&M Health Science Center College of Medicine, Dallas Campus, Dallas,
Texas (Vasudevan, Won, McCullough); Baylor Research Institute, Dallas, Texas
(Vasudevan, Won); Baylor University Medical Center, Dallas, Texas (Jazi, Ball,
Patankar, Sarmast, McCullough); Baylor Jack and Jane Hamilton Heart and
Vascular Hospital, Dallas, Texas (Ball, Won, Patankar, Sarmast, McCullough);
Division of Aging, Department of Medicine, Brigham and Women's Hospital/
Harvard Medical School, Boston, Massachusetts (Shin); Division of Cardiology,
Department of Medicine, VA Boston Health Care System, Boston, Massachusetts
(Shin); and The Heart Hospital Baylor Plano, Plano, Texas (McCullough).
Corresponding author: Anupama Vasudevan, BDS, MPH, PhD, Baylor Heart
and Vascular Institute, 621 N. Hall Street, Suite H030, Dallas, TX 75226 (e-mail:
Anupama.Vasudevan@BSWHealth.org).
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