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354 Iyngkaran et al. | Journal of Clinical and Translational Research 2023; 9(5): 347-356
disease. As there can be numerous confounders, this is an example observations have shaped new directions for therapy. As a specific
of why this approach is one-dimensional. In CHF, there are aspects theoretical example, we have contextualised the argument to smooth
of chronic disease care that cannot be mapped by traditional risk muscle and endothelium function. An area that is novel in clinical
scoring. For example, any patient can be at risk of decompensation medicine is identifying the sentinel common denominator of the
and resilience is hard to measure. Hence, it does pay to invest in effect to a treatment. This is vital for chronic diseases where there
high-value pathophysiological targets and explore their function are numerous confounders. While innovation remains critical, we
in multiple dimensions. Entropy appears as a common point that acknowledge that entropy in a clinical sense is theoretical, and our
shapes the direction of any individual to stress. The key question focus is on exploring what is known and reshaping new thinking
is which factor/s can be identified as the rate-limiting one, hence based on evidence. Bench-to-bedside research today can address
where is the starting point to channel research resources? common questions and find translatable answers. The margin to
Specifically on endothelium and skeletal muscle, endothelial maneuver, however, with clinical and basic sciences is decreasing in
dysfunction alters both cardiac and skeletal muscle function. some areas. Cost-effectiveness remains an important consideration
If the factor is oxidative stress which can be involved in the in health services. Specifically, in this paper, we ask the question
pathophysiology of HF in the heart as well as in the skeletal if we can identify higher risk patients, those who may not achieve
muscle; however, the downstream effects at each organ could the full benefits of GDMT, and are going in the direction that is
differ. The treatment effects could also differ. The direction in away from good health? In these cases, investment in conventional
which patients’ well-being moves could vary based on a broader guideline care will be costly with little progress. Alternatively, a
picture. Thus, where entropy is relevant, is that these processes common denominator can be identified to reverse this. Is there
might be predetermined, regardless of conventional risk score a common denominator here for treatment direction and how do
predictions. An ability to predict this will allow us to target the we address this? Improving health and reducing readmissions is
patients and deliver the intensive support that may be needed. a critical consideration as it relates to cost-effectiveness of health
A better understanding of these mechanisms may enable the policies. Simple Summary: Trial evidence extrapolates well to
development of novel and effective therapeutic strategies against large populations, it may be too complex to broaden applicability
HF, by targeting the factor least likely to respond to GDMT. further. New concepts that encourage and vet novel observations
More specifically, with CHF, there are pleiotropic actions of on clinical outcomes when delivering GDMTs are vital. Entropy is
conventional cardiovascular drugs that could play a greater role. a subjective common denominator to start a dialogue on the more

4.5. Observations and the personalisation of GDMT objective pathophysiology determinants in chronic and complex
care.
An ideal that is yet to take greater shape in medical practice
is personalised health parameters, it is hoped that it will achieve Acknowledgments
optimal individualisation of care. The terminology used varies None.
from personalised [46], customised [47], precision [48,49] care

for screening, disease management, and risk prognostication. The Funding
tools at hand help phenotypic and genetic profiling and presently None.
computer-assisted analysis of data are also possible. Leopold and
Loscalzo [49] that exactness can be counterproductive, thus, as Conflicts of Interest
opposed to only identifying the positive, should we identify what
does not work, we must invest in identifying causation. GDMT is a All authors have received government and non-governmental
checklist, and this can lead to polypharmacy without the intended funding. The authors declare no conflicts of interest.
benefits in some cases, or lack of benefits when treatments are References
deemed unsuitable. If cost-effectiveness is the standard objective
that guides universal systems of care, better use of medicines [1] McDonagh TA, Metra M, Adamo M, Gardner RS,
must be at the heart of this discussion. One place to start is the Baumbach A, Böhm M, et al. 2021 ESC Guidelines for
concept of entropy and identifying early common factors in the the Diagnosis and Treatment of Acute and Chronic Heart
failure of therapies. The cost of inefficacious medications is a Failure: Developed by the Task Force for the Diagnosis
preventable cost to health systems and patients, in the latter, they and Treatment of Acute and Chronic Heart Failure of the
can be expressed as disability-adjusted life years. We must thus be European Society of Cardiology (ESC) with the Special
mindful of Ehrlich’s predication and advance it with thinking on Contribution of the Heart Failure Association (HFA) of the
“It is because we are to exact, we may also fail.” ESC. Eur Heart J 2021;42:3599-726.
5. Conclusions [2] Heidenreich PA, Bozkurt B, Aguilar D, Allen LA, Byun JJ,
Colvin M, et al. 2022 AHA/ACC/HFSA Guideline for the
In this review, we discuss CHF, a chronic and complex Management of Heart Failure: A Report of the American
cardiovascular syndrome, and explore the paradigm in observing College of Cardiology/American Heart Association Joint
the delivery of GDMT. We have cited examples where post-trial Committee on Clinical Practice Guidelines. Circulation
DOI: http://dx.doi.org/10.18053/jctres.09.202305.23-00010