ESC Heart Failure,
Journal Year:
2023,
Volume and Issue:
10(5), P. 2998 - 3010
Published: Aug. 2, 2023
Abstract
Aims
Impaired
myocardial
energy
homeostasis
plays
an
import
role
in
the
pathophysiology
of
heart
failure
with
preserved
ejection
fraction
(HFpEF).
Left
ventricular
relaxation
has
a
high
demand,
and
left
diastolic
dysfunction
been
related
to
impaired
homeostasis.
This
study
investigated
whether
trimetazidine,
fatty
acid
oxidation
inhibitor,
could
improve
consequently
exercise
haemodynamics
patients
HFpEF.
Methods
results
The
DoPING‐HFpEF
trial
was
phase
II
single‐centre,
double‐blind,
placebo‐controlled,
randomized
cross‐over
trial.
Patients
were
trimetazidine
treatment
or
placebo
for
3
months
switched
after
2‐week
wash‐out
period.
primary
endpoint
change
pulmonary
capillary
wedge
pressure,
measured
right
catheterization
at
multiple
stages
bicycling
exercise.
Secondary
phosphocreatine/adenosine
triphosphate,
index
status,
phosphorus‐31
magnetic
resonance
spectroscopy.
included
25
(10/15
males/females;
mean
(standard
deviation)
age,
66
(10)
years;
body
mass
index,
29.8
(4.5)
kg/m
2
);
diagnosis
HFpEF
confirmed
(exercise)
either
before
during
There
no
effect
on
outcome
pressure
levels
(mean
0
[95%
confidence
interval,
95%
CI
−2,
2]
mmHg
over
exercise,
P
=
0.60).
Myocardial
triphosphate
arm
similar
(1.08
[0.76,
1.76]
vs.
1.30
[0.95,
1.86],
0.08).
by
compared
exploratory
parameters:
6‐min
walking
distance
−6
−18,
7]
m
−5
−22,
22]
m,
respectively,
0.93),
N‐terminal
pro‐B‐type
natriuretic
peptide
(5
(−156,
166)
ng/L
−13
(−172,
147)
ng/L,
0.70),
overall
quality‐of‐life
(KCCQ
EQ‐5D‐5L,
0.78
0.51,
respectively),
parameters
function
echocardiography
cardiac
resonance,
metabolic
parameters.
Conclusions
Trimetazidine
did
not
Circulation,
Journal Year:
2023,
Volume and Issue:
149(11), P. 860 - 884
Published: Dec. 28, 2023
BACKGROUND:
SGLT2
(sodium-glucose
cotransporter
2)
inhibitors
(SGLT2i)
can
protect
the
kidneys
and
heart,
but
underlying
mechanism
remains
poorly
understood.
METHODS:
To
gain
insights
on
primary
effects
of
SGLT2i
that
are
not
confounded
by
pathophysiologic
processes
or
secondary
to
improvement
SGLT2i,
we
performed
an
in-depth
proteomics,
phosphoproteomics,
metabolomics
analysis
integrating
signatures
from
multiple
metabolic
organs
body
fluids
after
1
week
treatment
nondiabetic
as
well
diabetic
mice
with
early
uncomplicated
hyperglycemia.
RESULTS:
Kidneys
reacted
most
strongly
in
terms
proteomic
reconfiguration,
including
evidence
for
less
proximal
tubule
glucotoxicity
a
broad
downregulation
apical
uptake
transport
machinery
(including
sodium,
glucose,
urate,
purine
bases,
amino
acids),
supported
mouse
human
interactome
studies.
affected
heart
liver
signaling,
more
reactive
included
white
adipose
tissue,
showing
lipolysis,
and,
particularly,
gut
microbiome,
lower
relative
abundance
bacteria
taxa
capable
fermenting
phenylalanine
tryptophan
cardiovascular
uremic
toxins,
resulting
plasma
levels
these
compounds
p-cresol
sulfate).
was
detectable
murine
stool
samples
its
addition
microbiota
fermentation
recapitulated
some
microbiome
findings,
suggesting
direct
inhibition
aromatic
acids
tryptophan.
In
lacking
patients
decompensated
failure
diabetes,
likewise
reduced
circulating
sulfate,
impaired
contractility
rhythm
induced
pluripotent
stem
cell–derived
engineered
tissue.
CONCLUSIONS:
formation
toxins
such
sulfate
thereby
their
exposure
need
renal
detoxification,
which,
combined
kidney
transporters
acid,
urate
uptake),
provides
foundation
protection.
Frontiers in Neuroendocrinology,
Journal Year:
2024,
Volume and Issue:
73, P. 101131 - 101131
Published: Feb. 16, 2024
This
systematic
review
and
meta-analysis
aimed
to
determine
the
association
between
use
of
sodium-glucose
cotransporter
2
(SGLT-2)
inhibitors
dementia
onset
as
well
cognitive
function
in
patients
with
diabetes
mellitus.
We
comprehensively
searched
MEDLINE,
Embase,
CENTRAL
databases
select
relevant
studies
published
up
August
2023.
The
SGLT-2
significantly
lowers
risk
compared
SGLT-2i
non-users
(Hazard
ratio:
0.68,
95
%
CI:
0.50-0.92).
Furthermore,
our
findings
indicated
a
positive
effect
inhibitor
on
score
improvement,
demonstrated
by
standardized
mean
difference
0.88
(95
0.32-1.44),
particularly
among
populations
mild
impairment
or
dementia.
indicate
potential
role
reducing
These
underscore
need
for
well-controlled
large
clinical
trials
future
research
this
field.
Cardio-Oncology,
Journal Year:
2025,
Volume and Issue:
11(1)
Published: Feb. 11, 2025
Abstract
More
evidence-based
strategies
are
needed
for
preventing
and
managing
cancer
treatment-related
cardiovascular
toxicity
(CTR-CVT).
Owing
to
the
growing
body
of
evidence
supporting
their
cardioprotective
role
in
several
cardiac
injury
scenarios,
sodium-glucose
cotransporter
2
inhibitors
(SGLT2i)
may
be
beneficial
treating
CTR-CVT.
In
October
2024,
a
search
was
conducted
PubMed
database
review
full
studies
investigating
SGLT2i
against
We
identified
44
published/pre-print
3
ongoing
randomised
controlled
trial
across
eight
types
treatment
(anthracyclines,
platinum-containing
therapy,
immune
checkpoint
inhibitors,
HER2-targeted
therapies,
kinase
androgen
deprivation
multiple
myeloma
therapies
5-fluorouracil).
Most
used
animal
models
focussed
on
primary
prevention.
43
found
some
effect
CTR-CVT,
which
cases
included
ejection
fraction
decline
aberrations
electrophysiological
parameters.
Some
also
observed
effects
mortality.
A
central
triad
anti-inflammatory,
anti-oxidative
anti-apoptotic
mechanisms
likely
underlie
SGLT2i-mediated
cardioprotection
Overall,
this
research
suggests
that
promising
candidate
CTR-CVT
either
as
monotherapy
or
combination
with
other
drugs.
However,
literature
is
limited
no
prospective
trials
prevention
management
exist
most
existing
human
retrospective
data
based
diabetic
populations.
Future
work
must
focus
addressing
these
limitations
current
literature.
Biomedicines,
Journal Year:
2025,
Volume and Issue:
13(3), P. 608 - 608
Published: March 3, 2025
Sodium-glucose
cotransporter-2
inhibitors
(SGLT2i),
initially
developed
as
antihyperglycemic
agents,
have
revolutionized
heart
failure
(HF)
management,
offering
substantial
benefits
across
all
stages
and
phenotypes
of
the
disease.
Regardless
left
ventricular
ejection
fraction
(LVEF),
these
agents
proven
efficacy
in
both
chronic
acute
HF
presentations.
This
review
explores
SGLT2i
applications
spanning
continuum,
from
early
(Stage
A)
at-risk
individuals
to
mitigation
progression
advanced
D).
Evidence
numerous
trials
has
shown
that
significantly
lower
rates
hospitalization,
improve
renal
function,
decreases
cardiovascular
mortality,
highlighting
their
multifaced
mechanisms
action
care.
also
highlights
potential
by
which
exert
beneficial
effects
on
systems,
each
contributing
sustained
clinical
improvements.
However,
integration
into
guideline-directed
medical
therapy
poses
practical
challenges,
including
initiation
timing,
dosing,
monitoring,
are
addressed
support
effective
treatment
adaptation
patient
populations.
Ultimately,
this
provides
a
comprehensive
assessment
foundational
HF,
emphasizing
role
an
intervention
multiple
aimed
at
improving
outcomes
entire
spectrum.
Pharmacology & Therapeutics,
Journal Year:
2025,
Volume and Issue:
270, P. 108861 - 108861
Published: April 15, 2025
Sodium-glucose
co-transporter
2
(SGLT2)
inhibitors
are
oral
antidiabetic
agents
that
have
shown
significant
improvements
in
cardiovascular
and
renal
outcomes
among
patients
with
heart
failure
(HF),
regardless
of
diabetic
status,
establishing
them
as
a
cornerstone
therapy.
In
addition
to
glycemic
control
the
osmotic
diuretic
effect,
inhibition
SGLT2
improves
endothelial
function
vasodilation,
optimizing
myocardial
energy
metabolism
preserving
cardiac
contractility.
Moreover,
may
exhibit
anti-inflammatory
properties
attenuate
acute
ischemia/reperfusion
injury,
thereby
reducing
infarct
size,
enhancing
left
ventricular
function,
mitigating
arrhythmias.
These
pleiotropic
effects
demonstrated
efficacy
across
various
conditions,
ranging
from
chronic
coronary
syndromes
extending
arrhythmias,
valvular
disease,
cardiomyopathies,
cardio-oncology,
cerebrovascular
disease.
This
review
provides
an
overview
current
literature
on
potential
mechanisms
underlying
effectiveness
wide
range
diseases
beyond
HF.
International Journal of Molecular Sciences,
Journal Year:
2023,
Volume and Issue:
24(5), P. 4321 - 4321
Published: Feb. 21, 2023
Heart
failure
is
a
complex
medical
syndrome
that
attributed
to
number
of
risk
factors;
nevertheless,
its
clinical
presentation
quite
similar
among
the
different
etiologies.
displays
rapidly
increasing
prevalence
due
aging
population
and
success
treatment
devices.
The
pathophysiology
heart
comprises
several
mechanisms,
such
as
activation
neurohormonal
systems,
oxidative
stress,
dysfunctional
calcium
handling,
impaired
energy
utilization,
mitochondrial
dysfunction,
inflammation,
which
are
also
implicated
in
development
endothelial
dysfunction.
with
reduced
ejection
fraction
usually
result
myocardial
loss,
progressively
ends
remodeling.
On
other
hand,
preserved
common
patients
comorbidities
diabetes
mellitus,
obesity,
hypertension,
trigger
creation
micro-environment
chronic,
ongoing
inflammation.
Interestingly,
dysfunction
both
peripheral
vessels
coronary
epicardial
microcirculation
characteristic
categories
has
been
associated
worse
cardiovascular
outcomes.
Indeed,
exercise
training
drug
display
favorable
effects
against
apart
from
their
established
direct
benefit.