Circulation. 2008;118:1217-1218
doi: 10.1161/CIRCULATIONAHA.108.190526
(Circulation. 2008;118:1217-1218.)
© 2008 American Heart Association, Inc.
Clinical Summaries
 |
Dose Effect of Clopidogrel Reloading in Patients Already on 75-mg Maintenance Dose: The Reload With Clopidogrel Before Coronary Angioplasty in Subjects Treated Long Term With Dual Antiplatelet Therapy (RELOAD) Study
|
|---|
The findings of the RELOAD study have relevant implications
for clinicians with regard to dosing issues of clopidogrel in
patients on a maintenance dose of 75 mg who are candidates for
an elective percutaneous coronary intervention. It was only
recently shown that a loading dose
600 mg may reduce hard events
within the first months of percutaneous coronary intervention
in clopidogrel-naïve patients, suggesting that poor response
to clopidogrel was a modifiable risk factor in the setting of
percutaneous coronary intervention. In addition, clopidogrel
at the approved maintenance dose of 75 mg has been shown to
achieve a modest antiplatelet effect, and up to one third of
patients may continue to have elevated platelet reactivity.
The RELOAD study supports the clinical use of a high clopidogrel
loading dose of 900 mg in patients undergoing percutaneous coronary
intervention even when patients already receive long-term therapy
of clopidogrel. In the clopidogrel-treated patients of the RELOAD
study, a single administration of 900-mg loading dose was the
only independent correlate of an optimal light transmission
aggregation response compared with 300- or 600-mg loading. This
regimen was associated with a dramatic reduction in poor response,
regardless of the definition used, within 4 hours of administration.
The results of RELOAD are consistent with those of other recent
studies supporting the use of a high loading dose of clopidogrel.
See p
1225.
|
Hot Flashes and Subclinical Cardiovascular Disease: Findings From the Study of Women’s Health Across the Nation Heart Study
|
|---|
The present study found impaired flow-mediated dilation and
higher aortic calcification among women at midlife reporting
menopausal hot flashes. Hot flashes, common during the menopausal
transition, have been viewed largely as a quality-of-life issue,
not a medical issue. Hot flashes have been of increased clinical
interest since findings of health risk associated with hormone
therapy. Although the cause of hot flashes remains incompletely
understood, recent findings from previous investigations have
suggested increased cardiovascular risk among subsets of women
reporting hot flashes. The present study examined associations
between hot flashes and several indices of subclinical cardiovascular
disease among 492 black and white midlife women. Results indicated
that relative to women not reporting hot flashes, women reporting
hot flashes had evidence of lower flow-mediated dilation, a
marker of poor endothelial function, and higher aortic calcification,
a measure of calcified plaques and arteriosclerotic remodeling
of the artery. These associations were evident in the sample
as a whole and were robust to adjustment for demographic and
known cardiovascular risk factors, as well as for serum estradiol
concentrations. Although the observed associations deserve further
replication and investigation, these findings suggest that in
addition to their impact on quality of life, hot flashes may
signal underlying adverse vascular changes among women transitioning
through menopause. See p
1234.
|
Effects of Continuous Aortic Flow Augmentation in Patients With Exacerbation of Heart Failure Inadequately Responsive to Medical Therapy: Results of the Multicenter Trial of the Orqis Medical Cancion System for the Enhanced Treatment of Heart Failure Unresponsive to Medical Therapy (MOMENTUM)
|
|---|
The Multicenter Trial of the Orqis Medical Cancion System for
the Enhanced Treatment of Heart Failure Unresponsive to Medical
Therapy (MOMENTUM) examined the effects of continuous aortic
flow augmentation, a novel percutaneous intervention, on hemodynamics
and clinical outcomes, randomizing patients hospitalized with
heart failure who were inadequately responsive to medical therapy
either to continued medical therapy, including intravenous diuretics
and inotropes and/or vasodilators, or to medical therapy plus
continuous aortic flow augmentation. On the basis of baseline
characteristics and overall mortality, MOMENTUM enrolled perhaps
the sickest acute heart failure population ever studied in a
randomized controlled trial. The trial confirmed hemodynamic
benefits for continuous aortic flow augmentation, with augmented
cardiac index and reduced pulmonary capillary wedge pressure
representing an upward-leftward Starling curve shift and denoting
improved left ventricular systolic performance. However, enrollment
ended early because of an inability to demonstrate significant
benefit on the primary hemodynamic-clinical composite end point
(device, 17.4%; control, 13.6%;
P=0.45) in the face of excess
device group bleeding. Thirty-five–day Kansas City Cardiomyopathy
Questionnaire Overall Summary scores increased by 38.4±22.7
and 31.2±26.0 points in the device and control groups,
respectively (between-group
P=0.10). Through 65 days, device-to-control
hazard ratios were as follows: all-cause mortality, 1.05 (95%
confidence interval, 0.60 to 1.82); death or heart failure hospitalization,
0.87 (95% confidence interval, 0.57 to 1.33); and heart failure
hospitalization, 0.66 (95% confidence interval, 0.38 to 1.13).
Major bleeds occurred in 16.5% in the device (7.3% treatment
related) and 5.1% in the control (
P=0.05) group. It has been
extraordinarily difficult to demonstrate clinical efficacy with
any intervention in a trial of patients hospitalized with heart
failure. Although MOMENTUM was no exception, the findings provide
direction for future investigation aimed at translating the
hemodynamic benefits of continuous aortic flow augmentation
into improved clinical outcomes. See p
1241.
|
Trimetazidine, a Metabolic Modulator, Has Cardiac and Extracardiac Benefits in Idiopathic Dilated Cardiomyopathy
|
|---|
Metabolic modulators such as trimetazidine have raised considerable
interest as additional forms of heart failure therapy. The concept
that such agents may optimize myocardial energy metabolism and
allow more efficient production of energy from glucose than
from free fatty acids is appealing. Trimetazidine has been studied
extensively in heart failure predominantly of ischemic origin.
We extend the previous findings by showing that trimetazidine
(1) improves left ventricular function in patients with chronic
heart failure caused by nonischemic dilated cardiomyopathy;
(2) reduces myocardial free fatty acid oxidation by only 10%
in the failing human heart, raising the possibility of additional
mechanisms of action; (3) has whole-body metabolic effects,
with increased insulin sensitivity potentially linked to decreased
whole-body free fatty acid oxidation; and (4) unexpectedly improves
circulating lipid profile by increasing high-density lipoprotein
cholesterol levels by 11%. The trimetazidine-induced improvement
in left ventricular function is linked to the degree of β-blockade,
suggesting an additive effect of these 2 therapies. Thus, trimetazidine
has both cardiac and extracardiac positive effects. Further
studies in heart failure testing combinations of metabolic modulators
active at different sites and during exercise are warranted.
See p
1250.
|
Combined Statin and Niacin Therapy Remodels the High-Density Lipoprotein Proteome
|
|---|
Intense interest exists in high-density lipoprotein (HDL) as
a target for therapies designed to prevent coronary artery disease
(CAD). Although most studies of HDL have focused on HDL cholesterol
levels, recent work has indicated that HDL carries a wide range
of previously unsuspected components. These include families
of proteins implicated in inhibiting proteolysis or activating
the complement system, and both factors are thought to be involved
in the pathogenesis of CAD. Moreover, control and CAD subjects
appear to carry different protein cargos on their HDL. In the
present studies, we used mass spectrometry to examine the protein
composition of HDL isolated from subjects with established CAD
before and during treatment with extended-release niacin and
atorvastatin, which elevate HDL cholesterol and reduce the risk
of CAD. Our observations indicate that this combination therapy
remodels the HDL proteome so that it resembles the proteome
of apparently healthy age- and sex-matched control subjects.
This finding raises the possibility that quantifying the HDL
proteome of CAD patients could provide insights into the therapeutic
efficacy of antiatherosclerotic interventions. See p
1259.
|
Perinatal Outcome of Fetal Atrioventricular Block: One-Hundred-Sixteen Cases From a Single Institution
|
|---|
Congenital atrioventricular block is a rare finding, occurring
in
1 in 11 000 to 20 000 live births. With the advent of fetal
echocardiography, congenital heart block has been identified
earlier in life. Even with more recent published data showing
larger fetal series, the natural course of the disease and late
follow-up remain unclear. Moreover, data are lacking that show
extensive evaluation of untreated fetuses that were serially
monitored with echocardiograms, which makes a critical appraisal
of the efficacy of steroid treatment inconclusive. A better
understanding of the spectrum and outcome of fetal atrioventricular
block would facilitate counseling of the parents, patient care,
and evaluation of newer therapies. To provide further information
on the outcome of fetal atrioventricular block, we describe
here the experience of a single institution with a large group
of untreated fetuses in a country where interruption of pregnancy
is not legally allowed. The consistency of information that
results from this long-term study from a single center is unique,
especially because we were able to trace the natural history
of atrioventricular block diagnosed during fetal life. The present
study also indicates that steroid therapy seems not to have
an effect on the natural history of fetal autoimmune-related
atrioventricular block and should help to improve the patient
selection for this kind of treatment. A large-scale, prospective,
multicenter trial addressing the efficacy and safety of this
treatment would be beneficial. See p
1268.
|
Vessel-Specific Toll-Like Receptor Profiles in Human Medium and Large Arteries
|
|---|
Inflammatory diseases of arteries, including atherosclerosis
and vasculitides, target certain regions of the vascular tree
while sparing others. This phenomenon suggests that arterial
beds respond to inflammatory stimuli with a vessel-specific
pattern. The immune system initiates inflammatory responses
after sensing "danger signals," often products released by infectious
microorganisms or by injured tissue. Here, we have tested human
medium-sized and large arteries for their ability to sense danger
signals and have compared arteries from different regions of
the body (aorta, temporal, carotid, subclavian, mesenteric,
and iliac arteries) for this function. Immune-sensing cells
use receptors from the Toll-like receptor (TLR) family to recognize
pathogen-associated patterns. Profiling of the 6 arterial beds
for the expression of TLR1 through TLR9 demonstrated abundant
expression of these receptors in all arteries; however, each
arterial territory expressed a unique TLR portfolio. Pathogen-sensing
receptors were localized primarily on cells in the adventitia
of the artery. Specifically, dendritic cells placed at the adventitia-media
border are responsible for this sensing function. In organ culture
and human arteries engrafted into immunodeficient mice, we confirmed
that pathogen-derived motifs stimulate dendritic cells embedded
deeply in the vessel wall and facilitate recruitment and in
situ activation of T lymphocytes. In essence, these data establish
that human macrovessels participate in immune monitoring and
that each arterial bed has a unique fingerprint of pathogen
receptors. The territorial distribution of TLR may contribute
to the tropism of inflammatory vasculopathies. See p
1276.
Related Articles:
-
Perinatal Outcome of Fetal Atrioventricular Block: One-Hundred-Sixteen Cases From a Single Institution
- Lilian M. Lopes, Gláucia Maria Penha Tavares, Ana Paula Damiano, Marco Antônio Borges Lopes, Vera Demarchi Aiello, Regina Schultz, and Marcelo Zugaib
Circulation 2008 118: 1268-1275.
[Abstract]
[Full Text]
-
Combined Statin and Niacin Therapy Remodels the High-Density Lipoprotein Proteome
- Pattie S. Green, Tomas Vaisar, Subramaniam Pennathur, J. Jacob Kulstad, Andrew B. Moore, Santica Marcovina, John Brunzell, Robert H. Knopp, Xue-Qiao Zhao, and Jay W. Heinecke
Circulation 2008 118: 1259-1267.
[Abstract]
[Full Text]
-
Effects of Continuous Aortic Flow Augmentation in Patients With Exacerbation of Heart Failure Inadequately Responsive to Medical Therapy: Results of the Multicenter Trial of the Orqis Medical Cancion System for the Enhanced Treatment of Heart Failure Unresponsive to Medical Therapy (MOMENTUM)
- Barry Greenberg, Barbara Czerska, Reynolds M. Delgado, Robert Bourge, Michael R. Zile, Marc Silver, Marc Klapholz, Ernest Haeusslein, Mandeep R. Mehra, Paul Mather, William T. Abraham, James D. Neaton, B. Scott Brown, Irene C. Parker, Marvin A. Konstam for the MOMENTUM Investigators and Coordinators
Circulation 2008 118: 1241-1249.
[Abstract]
[Full Text]
-
Dose Effect of Clopidogrel Reloading in Patients Already on 75-mg Maintenance Dose: The Reload With Clopidogrel Before Coronary Angioplasty in Subjects Treated Long Term With Dual Antiplatelet Therapy (RELOAD) Study
- Jean-Philippe Collet, Johanne Silvain, Antoine Landivier, Marie-Laure Tanguy, Guillaume Cayla, Anne Bellemain, Nicolas Vignolles, Sophie Gallier, Farzin Beygui, Ana Pena, and Gilles Montalescot
Circulation 2008 118: 1225-1233.
[Abstract]
[Full Text]
-
Hot Flashes and Subclinical Cardiovascular Disease: Findings From the Study of Women’s Health Across the Nation Heart Study
- Rebecca C. Thurston, Kim Sutton-Tyrrell, Susan A. Everson-Rose, Rachel Hess, and Karen A. Matthews
Circulation 2008 118: 1234-1240.
[Abstract]
[Full Text]
-
Trimetazidine, a Metabolic Modulator, Has Cardiac and Extracardiac Benefits in Idiopathic Dilated Cardiomyopathy
- Helena Tuunanen, Erik Engblom, Alexandru Naum, Kjell Någren, Mika Scheinin, Birger Hesse, K.E. Juhani Airaksinen, Pirjo Nuutila, Patricia Iozzo, Heikki Ukkonen, Lionel H. Opie, and Juhani Knuuti
Circulation 2008 118: 1250-1258.
[Abstract]
[Full Text]
-
Vessel-Specific Toll-Like Receptor Profiles in Human Medium and Large Arteries
- Olga Pryshchep, Wei Ma-Krupa, Brian R. Younge, Jörg J. Goronzy, and Cornelia M. Weyand
Circulation 2008 118: 1276-1284.
[Abstract]
[Full Text]
Top
Dose Effect of Clopidogrel...
Hot Flashes and Subclinical...