European Heart Journal,
Journal Year:
2023,
Volume and Issue:
44(37), P. 3640 - 3651
Published: June 13, 2023
For
decades,
heart
failure
with
preserved
ejection
fraction
(HFpEF)
proved
an
elusive
entity
to
treat.
Sodium-glucose
cotransporter
2
(SGLT2)
inhibitors
have
recently
been
shown
reduce
the
composite
of
hospitalization
or
cardiovascular
death
in
patients
HFpEF
landmark
DELIVER
and
EMPEROR-Preserved
trials.
While
improvements
blood
sugar,
pressure,
attenuation
kidney
disease
progression
all
may
play
some
role,
preclinical
translational
research
identified
additional
mechanisms
these
agents.
The
SGLT2
intriguingly
induce
a
nutrient-deprivation
hypoxic-like
transcriptional
paradigm,
increased
ketosis,
erythropoietin,
autophagic
flux
addition
altering
iron
homeostasis,
which
contribute
improved
cardiac
energetics
function.
These
agents
also
epicardial
adipose
tissue
alter
adipokine
signalling,
role
reductions
inflammation
oxidative
stress
observed
inhibition.
Emerging
evidence
indicates
that
drugs
impact
cardiomyocyte
ionic
homeostasis
although
whether
this
is
through
indirect
via
direct,
off-target
effects
on
other
ion
channels
has
yet
be
clearly
characterized.
Finally,
myofilament
stiffness
as
well
extracellular
matrix
remodelling/fibrosis
heart,
improving
diastolic
established
themselves
robust,
disease-modifying
therapies
recent
trial
results
are
incorporated
into
clinical
guidelines,
will
likely
become
foundational
therapy
HFpEF.
Circulation Research,
Journal Year:
2021,
Volume and Issue:
128(10), P. 1451 - 1467
Published: May 13, 2021
In
accordance
with
the
comorbidity-inflammation
paradigm,
comorbidities
and
especially
metabolic
are
presumed
to
drive
development
severity
of
heart
failure
preserved
ejection
fraction
through
a
cascade
events
ranging
from
systemic
inflammation
myocardial
fibrosis.
Recently,
novel
experimental
clinical
evidence
emerged,
which
strengthens
validity
inflammatory/profibrotic
paradigm.
This
consists
among
others
(1)
infiltration
by
immunocompetent
cells
not
only
because
an
obesity-induced
load
but
also
arterial
hypertension-induced
hemodynamic
load.
The
latter
is
sensed
components
extracellular
matrix
like
basal
laminin,
interact
cardiomyocyte
titin;
(2)
expression
in
cardiomyocytes
inducible
nitric
oxide
synthase
circulating
proinflammatory
cytokines.
results
accumulation
degraded
proteins
failing
unfolded
protein
response;
(3)
definition
machine
learning
algorithms
phenogroups
patients
distinct
signature;
(4)
direct
coupling
mediation
analysis
between
comorbidities,
inflammatory
biomarkers,
deranged
structure/function
endothelial
adhesion
molecules
already
apparent
early
preclinical
(HF
stage
A,
B).
new
paves
road
for
future
treatments
such
as
biologicals
directed
against
cytokines,
stimulation
ubiquitylation
phosphodiesterase
1
inhibitors,
correction
titin
stiffness
natriuretic
peptide-particulate
guanylyl
cyclase-PDE9
(phosphodiesterase
9)
signaling
molecular/cellular
regulatory
mechanisms
that
control
Nature,
Journal Year:
2023,
Volume and Issue:
619(7971), P. 801 - 810
Published: July 12, 2023
The
function
of
a
cell
is
defined
by
its
intrinsic
characteristics
and
niche:
the
tissue
microenvironment
in
which
it
dwells.
Here
we
combine
single-cell
spatial
transcriptomics
data
to
discover
cellular
niches
within
eight
regions
human
heart.
We
map
cells
microanatomical
locations
integrate
knowledge-based
unsupervised
structural
annotations.
also
profile
cardiac
conduction
system
Cardiovascular Research,
Journal Year:
2022,
Volume and Issue:
118(18), P. 3536 - 3555
Published: Aug. 24, 2022
Abstract
Many
patients
with
symptoms
and
signs
of
heart
failure
have
a
left
ventricular
ejection
fraction
≥50%,
termed
preserved
(HFpEF).
HFpEF
is
heterogeneous
syndrome
mainly
affecting
older
people
who
many
other
cardiac
non-cardiac
conditions
that
often
cast
doubt
on
the
origin
symptoms,
such
as
breathlessness,
or
signs,
peripheral
oedema,
rendering
them
neither
sensitive
nor
specific
to
diagnosis
HFpEF.
Currently,
management
directed
at
controlling
treating
comorbid
hypertension,
atrial
fibrillation,
anaemia,
coronary
artery
disease.
also
characterized
by
persistent
increase
in
inflammatory
biomarkers.
Inflammation
may
be
key
driver
development
progression
its
associated
comorbidities.
Detailed
characterization
pathways
provide
insights
into
pathophysiology
guide
future
management.
There
growing
interest
novel
therapies
specifically
designed
target
deregulated
inflammation
therapeutic
areas,
including
cardiovascular
However,
large-scale
clinical
trials
investigating
effectiveness
anti-inflammatory
treatments
are
still
lacking.
In
this
manuscript,
we
review
role
possible
implications
for
trials.
Circulation Research,
Journal Year:
2023,
Volume and Issue:
132(3), P. 379 - 396
Published: Feb. 2, 2023
The
cardiovascular
system
requires
iron
to
maintain
its
high
energy
demands
and
metabolic
activity.
Iron
plays
a
critical
role
in
oxygen
transport
storage,
mitochondrial
function,
enzyme
However,
excess
is
also
cardiotoxic
due
ability
catalyze
the
formation
of
reactive
species
promote
oxidative
damage.
While
mammalian
cells
have
several
redundant
import
mechanisms,
they
are
equipped
with
single
iron-exporting
protein,
which
makes
particularly
sensitive
overload.
As
result,
levels
tightly
regulated
at
many
homeostasis.
dysregulation
ranges
from
deficiency
overload
seen
types
disease,
including
heart
failure,
myocardial
infarction,
anthracycline-induced
cardiotoxicity,
Friedreich's
ataxia.
Recently,
use
intravenous
therapy
has
been
advocated
patients
failure
certain
criteria
for
deficiency.
Here,
we
provide
an
overview
systemic
cellular
homeostasis
context
physiology,
deficiency,
current
therapeutic
strategies,
future
perspectives.
