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Clinical Presentation and Management 177
of Acute Heart Failure

sive monitoring.Vasopressors used in this setting lengths of hospital stay (6.8 and 6.9 days) were sim-
include norepinephrine, high-dose dopamine (>5 ilar in the two treatment groups.
micrograms/kg/min), and vasopressin, and these Ularitide - Ularitide is a synthetic analogue of the re-
should be carefully titrated to achieve adequate nal vasodilatory natriuretic peptide urodilatin. A ran-
perfusion of vital organs.
domized trial found that ularitide caused short-term
• Mechanical cardiac support: Mechanical modali- hemodynamic effects but did not improve clinical
ties used in AHF setting include IABP, ECMO, or outcomes . The TRUE-AHF trial found no significant
short-term left ventricular assist devices.For se- difference in clinical outcomes at 48 hours based
lected patients with severe HFrEF (generally with upon a hierarchical composite end point. Cardiovas-
left ventricular ejection fraction <25 percent) with cular mortality rates were similar in the ularitide and
acute, severe hemodynamic compromise (cardio- placebo groups at a median follow-up of 15 months.
genic pulmonary edema with cardiogenic shock), Patients in the ularitide group had higher rates of hy-
nondurable mechanical support is an option as a potension and had slightly higher transient increases
“bridge to decision” or “bridge to recovery” . These in serum creatinine levels with greater reductions in
patients usually have a cardiac index less than 2.0 SBP and N-terminal pro-BNP levels.
L/min per m2, a systolic arterial pressure below Hypertonic saline plus furosemide - The rationale for
90 mmHg, and a PCWP above 18 mmHg, despite using hypertonic saline solution includes an osmotic
adequate pharmacologic therapy.
effect that might help optimize refilling of the intra-
vascular compartment during intravenous diuretic
INVESTIGATIONAL THERAPY FOR ACUTE therapy and increases in renal blood flow that might
HEART FAILURE promote diuretic action .A meta-analysis included
The following investigational therapies have shown nine randomized controlled trials comparing intra-
some promise but are not considered appropriate for venous hypertonic saline solution plus intravenous
routine treatment. furosemide to intravenous furosemide alone with the
following results:
Investigational vasodilators
• Analysis for all-cause mortality included five trials
Serelaxin - Relaxin is a naturally occurring human and found a survival benefit with combined hyper-
peptide vasodilator. Although an international ran- tonic saline solution plus furosemide compared to
domized controlled trial comparing 48-hour inter- furosemide alone (risk ratio [RR] = 0.57, 95% con-
venous infusion of serelaxin (recombinant human fidence interval [CI] 0.44-0.74). However, there was
relaxin-2) with placebo in patients with ADHF (with substantial heterogeneity among the studies (I2 =
any left ventricular ejection fraction)found improve- 66 percent) and no significant benefit remained if
ments in some clinical outcomes (including reduc- either of two trials was excluded.
tions in cardiovascular and all-cause mortality at six
months), a subsequent larger trial failed to confirm • Based upon pooled results from four trials, com-
a clinical benefit.The RELAX-AHF trial enrolled 1161 bined hypertonic saline solution plus furosemide
patients with ADHF and systolic blood pressure >125 decreased heart failure-related hospital readmis-
mmHg . Serelaxin improved one measure of dyspnea sion compared to furosemide alone (RR = 0.51; 95%
through day five and reduced average length of in- CI 0.35-0.75). However, there was moderate het-
dex hospital stay but did not improve the proportion erogeneity among studies (I2 = 58 percent) and no
of patients with moderate or marked improvement in significant benefit remained if either of two trials
dyspnea measured by Likert scale during the first 24 was excluded.
hours or readmission to the hospital within 60 days. • Analyses of length of hospital stay (seven trials),
The serelaxin group experienced a significantly lower weight loss (eight trials), and preservation of renal
rate of cardiovascular death (hazard ratio [HR] 0.63; function (serum creatinine) all favored therapy with
95% CI 0.41-0.96) and all-cause mortality (HR 0.83, combined hypertonic saline solution plus furose-
95% CI 0.43-0.93) at six months . mide versus furosemide alone, although there was
The RELAX-AHF-2 trial enrolled 6545 patients with marked heterogeneity among studies for each of
ADHF and systolic blood pressure >125 mmHg . these outcomes.
Cardiovascular mortality (8.7 and 8.9 percent) and Continuous aortic flow augmentation - Continuous
all-cause mortality (11.2 and 11.9 percent) rates at six aortic flow augmentation (CAFA) provides continu-
months were similar for serelaxin and placebo. Rates ous flow through the aorta that augments pulsatile
of worsening heart failure (6.9 and 7.7 percent) and cardiac output. CAFA does not increase cardiac out-

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