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Left ventricular geometry predicts risk of sudden cardiac arrest in
patients with severely reduced ejection fraction
Comment by Raul Mitrani,
MD
M
arkers of structural heart
disease such as left ven-
tricular hypertrophy or
abnormal left ventricular geometric
patterns have been associated with
increased risk of ventricular arrhyth-
mias and/or implantable defibrillator
shocks. This paper examined various
left ventricular geometric patterns
in adult patients with sudden car-
diac arrest from the Oregon Sudden
Unexpected Death Study and com-
pared the prevalence of these pat-
terns with those in a control group.
The authors demonstrated that ec-
centric hypertrophy, defined as an
increased left ventricular mass index
with normal relative wall thickness,
was found in 40.7% of patients with
sudden cardiac arrest compared
with 25.7% of controls (P = 0.025).
Furthermore, eccentric hypertrophy,
but not concentric hypertrophy, was
independently predictive of sudden
cardiac arrest, with odds ratio of
2.15 (CI, 1.08–4.29; P = 0.03).
The implications of this study are
that the risk for ventricular arrhyth-
mias in patients with left ventricular
dysfunction may be modulated by
the type of ventricular remodelling.
In the future, it would be interesting
to determine whether therapies that
restore left ventricular remodelling
to a more normal geometry subse-
quently lower arrhythmic risk.
Dr Mitrani is Director
of Clinical Cardiac
Electrophysiology,
and Director
of the Cardiac
Electrophysiology
Laboratory at University of Miami,
Miller School of Medicine, Miami.
It would be interesting to
determine whether
therapies that restore left
ventricular remodelling to a
more normal geometry
subsequently lower
arrhythmic risk.
Unresolved hypochloraemia, diuretic resistance,
and poor outcome in patients with acute HF
Comment by Clyde Yancy,
MD, MSc, MACC, FAHA, MACP
T
he dictum in heart failure has
always been that impaired so-
dium handling is a fundamen-
tal pathophysiological mechanism
that contributes to symptomatic left
ventricular dysfunction. Moreover,
the bedrock of HF practice has been
that excess sodium consumption
exacerbates heart failure and sodium
restriction alleviates heart failure. Yet,
the evidence to support this dictum is
less evident andmore empiric. It is, in
fact, no longer heretical to suggest that
sodium restriction is at best dubious in
heart failure andmay even be harmful.
Some among us have even explored
salt administration as a therapeutic
option and have argued the potential
for benefit. Is there a truth embedded
in this discombobulation?
Perhaps a new dictum might be
entertained. Chloride, as in “sodium
chloride,” is not a passive electrolyte.
Renal salt sensing is dependent on
chloride rather than sodium, and an
emerging class of chloride-sensitive
kinases appear to establish a link
between renal tubule sodium han-
dling and neurohormonal activation.
Newly published data by Testani
and colleagues
1,2
stakes a new po-
tential truth – hypochloraemia has a
stronger association with clinical out-
comes and diuretic resistance than
sodium, and repletion of chloride
may reverse surrogates of diuretic
resistance. However, this is not the
eureka moment. The presented data
do not establish causality, repletion of
chloride does not improve outcomes
as of yet, and hypochloraemia may
be yet another epiphenomenon. But
making a pivot along a more promis-
ing path of investigation is a needed
catalyst to address the data void that
sodium chloride homeostasis in heart
failure now represents.
We are a long way from advising
chloride supplements as treatment
for heart failure. We should remain
aligned with rigorous sodium restric-
tion for those at risk for heart failure
and reasonable sodium restriction for
symptomatic patients. In the absence
of evidence, we should resist non-ev-
idence based approaches, including
salt loading, as treatment for heart
failure. But these data and multiple
other data points and commentaries
in the literature resonate with a very
clear message: it is now time to come
to a new point of sobriety. We know
very little about salt in heart failure;
before pursuing yet another elegant
pathophysiological pathway leading
to a new treatment “breakthrough,”
maybe we should critically explore
what we once thought was sacrosanct
– sodium restriction in heart failure.
It is time for a very different discovery
paradigm in heart failure: salt – we
need to know more.
References
1. Ter Maaten JM, Damman K, Hanberg
JS, et al Hypochloremia, Diuretic Re-
sistance, and Outcome in Patients With
Acute Heart Failure.
Circ Heart Fail
2016;9:e003109.
2. Hanberg JS, Rao V, Ter Maaten JM, et
al.
Circ Heart Fail
2016;9:e003180.
Dr Yancy is Vice Dean, Diversity
& Inclusion, Magerstadt Professor
of Medicine, Professor of Medical
Social Sciences, Chief, Division
of Cardiology, Northwestern
University, Feinberg School of
Medicine; Associate Director,
Bluhm Cardiovascular Institute,
Northwestern Memorial
Hospital, Chicago, Illinois.
Left ventricular geometry and risk of sudden cardiac arrest in patients with
severely reduced ejection fraction
Journal of the American Heart Association
Take-home message
•
In this study, 172 cases of sudden cardiac arrest (SCA) from the Oregon Sudden Unexpected Death Study and
74 geographic controls with no history of SCA and their archived echocardiograms were evaluated. This analysis
included patients with LVEF ≤40%. SCA cases had significantly lower LVEF, fewer had normal LV geometry, and
more had eccentric hypertrophy compared with controls. Eccentric hypertrophy was found to be predictive of SCA
in a multivariate model.
•
These findings demonstrate the potential for improved SCA risk determination based on routine echocardiograms.
Abstract
BACKGROUND
Recent reports indicate that specific left ven-
tricular (LV) geometric patterns predict recurrent ventricular
arrhythmias in patients with implantable cardioverter-defibril-
lators and reduced left ventricular ejection fraction (LVEF).
However, this relationship has not been evaluated among
patients at risk of sudden cardiac arrest (SCA) in the general
population.
METHODS AND RESULTS
Adult SCA cases from the Oregon
Sudden Unexpected Death Study were compared with
geographic controls with no prior history of SCA. Archived
echocardiograms performed closest and prior to the SCA
event were reviewed. LV geometry was defined as normal
(normal LV mass index [LVMI] and relative wall thickness
[RWT]), concentric remodeling (normal LVMI and increased
RWT), concentric hypertrophy (increased LVMI and RWT), or
eccentric hypertrophy (increased LVMI and normal RWT).
Analysis was restricted to those with LVEF ≤40%. A total
of 246 subjects were included in the analysis. SCA cases
(n=172, 68.6±13.3 years, 78% male), compared to controls
(n=74, 66.8±12.1 years, 73% male), had lower LVEF (29.4±7.9%
vs 30.8±6.3%, P=0.021). Fewer cases presented with normal
LV geometry (30.2% vs 43.2%, P=0.048) and more with eccen-
tric hypertrophy (40.7% vs 25.7%, P=0.025). In a multivariate
model, eccentric hypertrophy was independently predictive
of SCA (OR 2.15, 95% CI 1.08–4.29, P=0.03).
CONCLUSIONS
Eccentric LV hypertrophy was independently
associated with increased risk of SCA in subjects with EF
≤40%. These findings, now consistent between device-im-
planted and non-implanted populations, indicate the potential
of improving SCA risk stratification from the same noninvasive
echocardiogram at no additional cost.
J Am Heart Assoc
2016;5:e003715, Phan D, Aro AL, Reinier
K, et al.
Hypochloraemia, diuretic resistance, and outcome
in patients with acute heart failure
Circulation: Heart Failure
Take-home message
•
The authors evaluated the association between chloride levels and diuretic
responsiveness, decongestion, and mortality in 2033 patients hospitalised
for acute heart failure (HF) in the PROTECT trial. Baseline hypochloraemia
was associated with elevated bicarbonate, poor diuretic response, less
haemoconcentration, and worsening HF. Hypochloraemia developing
by day 14 was associated with declining renal function, increasing BUN
(P < 0.01), and increased mortality (P < 0.001).
•
These data indicated that chloride measurement in acute HF patients at
admission and at 14 days could be used as a marker for response to therapy
and outcome.
Abstract
BACKGROUND
Chloride plays a role in
renal salt sensing, neurohormonal acti-
vation, and regulation of diuretic targets,
and hypochloraemia predicts mortality
in acute heart failure (AHF). AHF thera-
pies, such as diuretics, alter chloride
homeostasis. We studied the association
between (changes in) chloride levels and
diuretic responsiveness, decongestion,
and mortality in patients with AHF.
METHODS AND RESULTS
Patients hos-
pitalized for AHF in the PROTECT
trial (n=2033) with serum chloride levels
within 24 hours of admission and 14 days
later were studied (n=1960). Hypochlo-
raemia was defined as serum chloride
<96 mEq/L. Mean baseline chloride was
100.8±5.0 mEq/L. Low baseline chloride
was associated with high bicarbonate,
poor diuretic response, less haemo-
concentration, and worsening heart
failure (all P < 0.01). Newly developed
hypochloraemia at day 14 was com-
mon and associated with a decline in
renal function and an increase in blood
urea nitrogen (P < 0.01). In multivariable
analyses, chloride measured at day 14,
but not baseline chloride, was strongly
and independently associated with
mortality through 180 days (hazard
ratio per unit decrease: 1.07 [1.03–1.10];
P < 0.001). In comparison, sodium was
not significantly associated with mortality
after multivariable adjustment at any time
point. Hypochloraemia at baseline that
resolved was not associated with mortal-
ity (P = 0.55), but new or persistent hy-
pochloraemia at day 14 was associated
with increased mortality (hazard ratio: 3.11
[2.17–4.46]; P < 0.001).
CONCLUSIONS
Low serum chloride at
AHF hospital admission was strongly
associated with impaired decongestion.
New or persistent hypochloraemia 14
days later was independently associ-
ated with reduced survival, whereas
hypochloraemia that resolved by day
14 was not.
Circ Heart Fail
2016;9:e003109, Ter
Maaten JM, Damman K, Hanberg JS
et al.
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HEART FAILURE & TRANSPLANTATION
VOL. 1 • No. 2 • 2016
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