ESC Congress 2017 In Review -- Main Edition - 24

Selected Content

Whether this classification or others, such as a proposed staging system of HF that is similar to the TNM-like
system used in cancer [Fedele F et al. J Am Coll Cardiol.
2014], could be useful for AHF remain unclear. A potentially useful clinical approach for AHF in the ESC 2016
guidelines is based on congestion and hypoperfusion
(Figure 2). Other factors useful in the initial assessment
and management of AHF include clinical severity, blood
pressure, heart rate/rhythm, and comorbidities.
Figure 2. Clinical Profiles of AHF Patients Based on Congestion and
Hypoperfusion
CONGESTION (-)

CONGESTION (+)
Pulmonary congestion
Orthopnoea/paroxysmal nocturnal
dyspnoea
Peripheral (bilateral) oedema
Jugular venous dilatation
Congested hepatomegaly
Gut congestion, ascites
Hepatojugular reflux

HYPOPERFUSION (-)

HYPOPERFUSION (+)
Cold sweated extremities
Oliguria
Mental confusion
Dizziness
Narrow pulse pressure

WARM-DRY

WARM-WET

COLD-DRY

COLD-WET

Reprinted from Ponikowski P, Voors AA et al. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2016;37:2129-
2200. doi:10.1093/eurheartj/ehw128. By permission of Oxford University Press
on behalf of the European Society of Cardiology.

More knowledge of the epidemiology of HF is crucial.
Studies from different countries have highlighted the
need for standardised definitions and clinical indications
for AHF. The global data that will accrue in the REPORTHF Registry [Filippatos G et al. Eur J Heart Fail. 2015] will
hopefully improve the situation.
The pathophysiology of AHF is also unclear, which has
hindered the development of diagnostic tools. Having a
proven diagnostic tool, like electrocardiography that is
used for acute myocardial infarction (AMI), is the goal of
AHF. Improvement in disease management is also needed.
Patients discharged with congestion are significantly
more likely to die within the next year than those discharged without pulmonary or peripheral congestion [Metra
M et al. Circ Heart Fail. 2012]. The complex pathophysiology of AHF makes it unlikely that a single target, like
thrombus in AMI, will be involved in AHF.
Pharmacologic treatment of AHF involves diuretics
to reduce fluid volume, vasodilators, and, if needed, inotrope-mediated augmentation of contractility. Trials are
underway to evaluate new drugs. Further on the horizon, wireless monitoring of pulmonary arterial pressure
is being explored.

October 2017

Other future therapeutic approaches were discussed
by Marco Metra, MD, University of Brescia, Brescia,
Italy. Ultrafiltration is being refined as a decongestion
strategy [Costanzo MR et al. J Am Coll Cardiol. 2017].
Definitive clinical trial data is lacking with the premature termination of the AVOID-HF trial [Costanzo MR et
al. JACC Heart Fail. 2016] due to slower than expected
enrolment. The PURE-HF trial [NCT03161158] which is
designed to evaluate whether tailored, peripheral ultrafiltration complementary to low-dose diuretics is associated with a reduction in cardiovascular mortality and HF
will hopefully provide evidence-based rigour.
Intravenous inotropes are not currently recommended,
except for symptomatically hypotensive or hypoperfused
patients, due to increased mortality in analyses from clinical trials. But, earlier data indicated a benefit of levosimendan in advanced HF [Parissis JT et al. Heart. 2006; Parissis
JT et al. J Am Coll Cardiol. 2006]. Ambulatory treatment
involving pulsed infusions of levosimendan did not improve
the primary outcomes, though with favourable effects on
quality of life and a tendency to reduced hospitalisations
[Altenberger J et al. Eur J Heart Fail. 2014]. However, a
recent meta-analysis has suggested a reduction in hospitalisations with repeated infusions [Silvetti S et al. ESC
Heart Fail. 2017] supporting the idea that more research on
inotropes is warranted.
Another approach is the oral use of omecamtiv
mecarbil, a drug that targets the cardiac protein myosin
to increase the duration of ejection time. Benefits were
demonstrated in the phase 2 COSMIC-HF trial [Teerlink
JR et al. Lancet. 2016]. The phase 3 GALACTIC-HF trial
[EudraCT number 2016-002299-28], designed to determine if treatment with omecamtiv mecarbil when added
to standard of care is well tolerated and reduces the risk
of cardiovascular death or HF events in patients with
chronic HFrEF, is underway.
Other drugs in earlier stages of development include
the second-generation nitroxyl donor, BMS-986231, for
treatment of HFrEF [Tita C et al. Eur J Heart Fail. 2017],
the partial adenosine A1-receptor agonist, capadenoson,
shown to improve left ventricular function in an experimental model [Sabbah HN. Eur J Heart Fail. 2016], and
targeted treatment of mitochondrial dysfunction using
elamipretide [Sabbah HN. Eur J Heart Fail. 2016].
Regenerative therapy may someday be used to rebuild
myocardial tissue that is defective. The results with stem
cell therapies for other applications certainly indicate the
potential of this approach. The CHART-1 trial of cardiopoietic regenerative therapy in congestive HF has been recently
concluded [Bartunek J et al. Eur J Heart Fail. 2016] and an
exploratory analysis identified a subgroup of patients who
may benefit from cardiopoietic cell therapy. The CHART-2
trial [NCT02317458] will further explore this therapy in
patients with chronic HF secondary to ischaemic cardiomyopathy.

medicom-publishers.com/mcr

http://www.medicom-publishers.com/mcr

Table of Contents for the Digital Edition of ESC Congress 2017 In Review -- Main Edition