Circulation. 2008;118:105-106
doi: 10.1161/CIRCULATIONAHA.108.189734
(Circulation. 2008;118:105-106.)
© 2008 American Heart Association, Inc.
Clinical Summaries
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Inadequate Blood Glucose Control Is Associated With In-Hospital Mortality and Morbidity in Diabetic and Nondiabetic Patients Undergoing Cardiac Surgery
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Our study demonstrates that inadequate blood glucose control
(BGC) after cardiac surgery is not specific to patients with
diabetes mellitus (DM). Inadequate BGC, regardless of DM status,
was independently associated with in-hospital mortality and
morbidity. Our findings have epidemiological, clinical, academic,
and financial implications. We suggest that DM patients represent
only a fraction of those suffering derangement of glucose metabolism
after surgery. The projected future number of adults with DM
is an underestimate of the number likely to be affected by deranged
glucose metabolism and its related complications. Inadequate
BGC after surgery seems to represent a separate clinical entity
that is explained only partially by undiagnosed and diet-controlled
diabetes. Our data suggest that strict protocols to maintain
BGC should be used for all patients. However, the efficacy of
these protocols and the pathophysiologic mechanisms of this
condition need further research. In addition, further research
and guidelines as to how best to manage these patients are needed.
Currently, important clinical decisions such as choice of screening
test, strategy for maintaining adequate BGC, and the ideal target
level of BGC are often left to the individual clinician. This
has resulted in inconsistencies in the definition of undiagnosed
DM, stress hyperglycemia, and inadequate BGC; marked variation
in estimates of prevalence; and significant variation in treatment,
the impact of which remains uncertain. Our findings also may
apply to patients admitted for major noncardiac surgery. The
impact on life expectancy and on hospital resources is potentially
enormous. See p
113.
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Prediction of First Events of Coronary Heart Disease and Stroke With Consideration of Adiposity
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The key determinants of cardiovascular disease (CVD) are age,
sex, cholesterol, high-density lipoprotein cholesterol, systolic
blood pressure level, cigarette smoking, and diabetes mellitus.
Greater adiposity generally has not been associated with the
development of CVD when the traditional variables mentioned
above are used to predict outcome. Data from 24 years of follow-up
for the Framingham Offspring Study population sample were used
to estimate the effect of body mass index (BMI) on risk of CVD.
In a simple prediction model of CVD that included age, sex,
and smoking, a 1-SD unit (4.33 kg/m
2) of BMI imparted a 28%
effect on risk of initial CVD events. After full adjustment
with the traditional CVD prediction factors, the effect of an
SD of BMI remained statistically significant but declined to
10%. It was estimated that 67% of the BMI effects appear to
operate through the ratio of cholesterol to high-density lipoprotein
cholesterol, systolic blood pressure, and diabetes mellitus.
These results imply that a considerable portion of the adverse
effects of BMI are exerted through traditional metabolic risk
factors and that long-term follow-up of middle-aged adults was
required to fully identify these effects. See p
124.
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Outcome of Alcohol Septal Ablation for Obstructive Hypertrophic Cardiomyopathy
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As an alternative mode of therapy for patients with symptomatic
obstructive hypertrophic cardiomyopathy, alcohol septal ablation
has emerged and is increasingly being performed in centers worldwide.
However, there continue to be questions about the efficacy of
septal ablation, particularly when compared with septal myectomy.
In this study, which was performed at a single tertiary hypertrophic
cardiomyopathy referral center, the overall survival after either
septal ablation or myectomy was similar. Septal ablation was
associated with a higher rate of acute complications. Survival
free of severe symptoms also was comparable in the overall population,
but patients
65 years of age had a lower rate of persistent
or recurrent symptoms if they had myectomy. Septal ablation
is an efficacious procedure if performed in an experienced institution
and may improve symptoms in a subset of patients with obstructive
hypertrophic cardiomyopathy. However, the in-hospital complication
rate is higher with septal ablation and symptom relief is better
with myectomy, especially in younger patients. These findings
should be considered when the choice of septal reduction therapy
is offered to hypertrophic cardiomyopathy patients. Long-term
follow-up is required to determine the ultimate role of ablation
in the treatment algorithm of these patients with hypertrophic
cardiomyopathy. See p
131.
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In Vivo Monitoring of Inflammation After Cardiac and Cerebral Ischemia by Fluorine Magnetic Resonance Imaging
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Currently, neither a clinically useful method to assess local
inflammatory processes associated with the risk of plaque rupture
nor a robust imaging method that provides information about
local activity of inflammation (which plays a crucial role in
various cardiovascular disease states such as ischemia/reperfusion,
myocarditis, transplant rejection, or stroke) is available.
In the present study, we demonstrate in murine models of myocardial
and cerebral ischemia that nanoemulsions of perfluorocarbons
can be used to precisely visualize localized inflammatory processes
as hot spots by simultaneous acquisition of morphologically
matching proton (
1H) and fluorine (
19F) magnetic resonance images.
Injected perfluorocarbons are phagocytized primarily by monocytes/macrophages,
resulting in
19F magnetic resonance imaging intensity signals
along the border of infarcted areas as a result of progressive
infiltration of the labeled immunocompetent cells. Because of
the lack of any
19F background in the body, observed signals
are robust and exhibit an excellent degree of specificity. Perfluorocarbons
are biologically inert and have been shown to be nontoxic in
humans. Thus,
19F MRI has the potential to be clinically applicable
as a new diagnostic modality not only for acute but also for
chronic inflammatory processes such as plaques in atherosclerosis.
See p
140.
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Longitudinal Tracking of Recipient Macrophages in a Rat Chronic Cardiac Allograft Rejection Model With Noninvasive Magnetic Resonance Imaging Using Micrometer-Sized Paramagnetic Iron Oxide Particles
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Numerous studies have shown that immune cells including macrophages
play crucial roles in the development of organ rejection. The
ability to monitor the migration and localization of specific
cell types in vivo, noninvasively, and in real time will greatly
improve our understanding of the complex roles that different
cells play in cardiac allograft rejection. This study presents
the feasibility of imaging individual recipient macrophages
in vivo by magnetic resonance imaging over long periods of time
in a rodent heterotopic working-heart transplantation model
with the use of a sensitive contrast agent, micrometer-sized
paramagnetic iron oxide particles. In this study, recipient
cells, mainly macrophages, have been labeled in vivo by direct
intravenous administration of micrometer-sized paramagnetic
iron oxide particles before heart transplantation. This cell-labeling
procedure is convenient for clinical application. Thus, this
approach provides a novel methodology for studying the mechanisms
of cardiac allograft rejection in both animals and humans. Moreover,
the current gold standard for diagnosing and staging rejection
after organ transplantation is biopsy, which is not only invasive
but also prone to sampling errors because rejection sites are
highly heterogeneous. The activated macrophages have been found
to be the primary cells in the cellular infiltrate of rejecting
grafts. Thus, this imaging modality using magnetic resonance
imaging to monitor cell migration in real time, with whole-heart
visualization of cellular infiltration, could potentially lead
to a powerful clinical tool, providing information for noninvasive
evaluation of graft rejection, managing treatment, and predicting
outcomes after heart transplantation. See p
149.
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Specific Jagged-1 Signal From Bone Marrow Microenvironment Is Required for Endothelial Progenitor Cell Development for Neovascularization
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Although accumulating evidence has indicated that therapy with
endothelial progenitor cells (EPCs) could be a promising modality
for vascular regeneration, the problems of quantity and quality
control need to be resolved to achieve translational application
in humans. Pathological conditions such as aging, diabetes mellitus,
and hypercholesterolemia lead to a decrease in circulating EPCs
and impairment of their proliferative and migratory function.
These limitations may be solved by the integration of both in
vitro expansion and quality control of EPCs by genetic modification,
such as transducing vascular endothelial growth factor, glycogen
synthase kinase-1β, human telomerase reverse transcriptase
expression, or adjunctive cytokines that promote EPC mobilization.
The promise of our therapeutic strategy is that governed Notch
signaling in culture can produce the preferred quality and quantity
of EPCs needed to enhance vasculogenic potential. The manipulation
of Jag-1 ligand–mediated signals in culture before transplantation
would allow EPCs to increase in number and augment their vasculogenic
potential in patients with ischemic diseases. See p
157.
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Hypoxia-Inducible Factor-1 Is Central to Cardioprotection: A New Paradigm for Ischemic Preconditioning
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During the past decade, very exciting research efforts have
revealed a central role of hypoxia-inducible factor (HIF) in
mammalian oxygen homeostasis. In addition to its role in increasing
erythropoietin production in response to limited oxygen availability,
many other adaptive responses to hypoxia were found to be regulated
by HIF, including metabolic adaptation, vascular angiogenesis,
and attenuation of inflammatory hypoxia. In the present studies,
we explored the hypothesis that HIF-1 also is central to ischemic
preconditioning of the heart. Our results provide pharmacological
and genetic evidence for a central role of HIF-1 in myocardial
adaptive processes elicited by ischemic preconditioning. These
studies also suggest pharmacological strategies to activate
HIF in the treatment of myocardial ischemia. The use of prolylhydroxylase
inhibitors appears to be a particularly promising pharmacological
approach. However, many questions remain about the use of HIF
activators. For example, the potential consequences of HIF activation
on the risk of de novo or recurrent neoplastic diseases have
to be thoroughly addressed before clinical use in humans. HIF
activators also are associated with dramatic increases in hematocrit
and circulating red cell volume, which may carry the risk of
acute thromboembolic complications. Nevertheless, HIF activators,
particularly the prolylhydroxylase inhibitors, represent a group
of novel therapeutic agents that have great therapeutic potential
in the treatment of conditions characterized by the acute need
of tissues to adapt to hypoxia such as that which occurs during
inflammatory bowel disease, stroke, renal ischemia, or myocardial
infarction. Thus, these compounds could cover a very wide range
of clinical applications. See p
166.
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