Circulation. 2008;118:1403-1404
doi: 10.1161/CIRCULATIONAHA.108.190528
(Circulation. 2008;118:1403-1404.)
© 2008 American Heart Association, Inc.
Clinical Summaries
 |
Two-Year Survival and Mental and Psychomotor Outcomes After the Norwood Procedure: An Analysis of the Modified Blalock-Taussig Shunt and Right Ventricle–to–Pulmonary Artery Shunt Surgical Eras
|
|---|
The outcomes of patients with hypoplastic left heart syndrome
treated with the Norwood procedure over 2 consecutive surgical
eras (1996 to 2002 and 2002 to 2005) were evaluated. Survival
in the early postoperative period and at 2 years of age demonstrated
improvement. Neurodevelopmental outcomes at 2 years of age (mental
and psychomotor developmental indices) showed improvement in
the more recent era, with psychomotor delay decreasing by half.
For these outcomes, we have identified independent predictors,
including modifiable variables, that may be important in guiding
clinical care management. For survival outcome at 2 years of
age, postoperative lactate was identified as an independent
predictor, which supports the longstanding clinical practice
aimed at optimizing patient hemodynamic status. For neurodevelopmental
outcomes, the identified independent negative predictors included
prolonged hospitalization and preoperative ventilation. We also
identified other independent outcome predictors that may play
an important role in parental counseling on anticipated neurodevelopmental
outcome. Such findings may allow the clinician to tailor parent
counseling by considering specific patient characteristics,
such as the need for cardiopulmonary resuscitation, as well
as sex and the family’s socioeconomic status. Finally,
early intervention and close multidisciplinary follow-up are
instrumental for these children at risk for adverse neurodevelopmental
outcomes. See p
1410.
|
Patent Foramen Ovale and Migraine: A Cross-Sectional Study From the Northern Manhattan Study (NOMAS)
|
|---|
Although a causal relationship between patent foramen ovale
(PFO) and migraine has been hypothesized, and improvement of
migraine severity after percutaneous PFO closure has been reported,
population-based data on this relationship are sparse. This
study reports on the lack of a significant association between
migraine and PFO detected with transthoracic echocardiography
and agitated saline among 1101 stroke-free elderly individuals
derived from an urban, population-based, multiethnic cohort.
In this population, the prevalence of self-reported migraine
was 16% (13% migraine with aura); the prevalence of PFO was
15%, and 2% of all individuals had migraine and PFO. Migraine
was significantly more frequent among younger individuals, women,
and Hispanics. The observed lack of association between PFO
and migraine (with or without aura) was not modified by other
traditional risk factors such as diabetes mellitus, hypertension,
cigarette smoking, or dyslipidemia. This study demonstrates
that PFO and migraine are relatively frequent conditions in
the general population, but their coexistence in an individual
is uncommon. Although this study did not evaluate the effect
of PFO closure, it indirectly supports the notion that the role
of PFO closure among patients with refractory migraine is questionable,
because a "true" relationship between PFO and migraine remains
uncertain. See p
1419.
|
Pilot Trial on Determinants of Progenitor Cell Recruitment to the Infarcted Human Myocardium
|
|---|
This study investigates homing of radioactively labeled circulating
progenitor cells into the infarct territory after intracoronary
infusion into the infarct-related artery in patients after myocardial
infarction. The salient findings are that the temporal proximity
to the ischemic event, the extent of myocardial necrosis, and
the magnitude of functional impairment of the coronary microcirculation
are individually likely to determine an increased uptake and
short-term retention of progenitor cells administered into the
infarct-related coronary artery. These findings may indicate
that the inflammatory processes ignited by the infarcted and
necrotic myocardium may play a major role in the recruitment
of progenitor cells into the ischemic tissue. Consequently,
when the inflammatory activation of the coronary vasculature
subsides during infarct healing and scar formation, recruitment
and homing of intravascularly administered progenitor cells
may be reduced. See p
1425.
|
Transition From Chronic Compensated to Acute Decompensated Heart Failure: Pathophysiological Insights Obtained From Continuous Monitoring of Intracardiac Pressures
|
|---|
The purpose of this study was to examine the pathophysiology
of chronic compensated and acute decompensated heart failure
(HF) in patients with systolic HF (SHF) versus patients with
diastolic HF (DHF). In this study, continuous measurements of
intracardiac pressures were made during periods of compensation,
during the development of acute decompensation, and after effective
treatment returned patients to a compensated state. This study
showed that significant structural and functional differences
exist between patients with SHF and those with DHF. However,
elevated diastolic filling pressures play a pivotal role in
the underlying pathophysiology of chronic compensated HF in
both SHF and DHF. Acute decompensation in both DHF and SHF patients
was preceded by a significant increase in diastolic pressures,
which occurred >2 weeks before hospitalization for HF. In
contrast, the patients who did not develop acute decompensated
HF had no significant changes in diastolic filling pressures.
In addition, effective treatment of acute decompensated HF resulted
in improved diastolic filling pressures. Intracardiac hemodynamic
monitoring may prove to be helpful in preventing and treating
acute decompensated HF. Therefore, an increased understanding
of the underlying pathophysiology of chronic compensated and
acute decompensated HF in both SHF and DHF should allow us to
develop more effective treatment and prevention strategies for
all HF patients. See p
1433.
|
Cerebrovascular Thromboprophylaxis in Mice by Erythrocyte-Coupled Tissue-Type Plasminogen Activator
|
|---|
Cerebrovascular thrombosis is a major cause of mortality and
morbidity, including after surgery when the use of thromboprophylaxis
is limited by the formidable risk of perioperative bleeding.
Nor can thrombolytics (eg, tissue-type plasminogen activator
[tPA]) be used prophylactically in this and other high-risk
settings because of their short duration of action and risk
of causing hemorrhage. Coupling tPA to red blood cells (RBCs)
prolongs and confines activity within the bloodstream and enhances
resistance to plasma inhibitors, thereby providing a novel thromboprophylactic
agent, RBC/tPA. Our results indicate that injection of RBC/tPA
into mice before thromboembolic occlusion of the middle carotid
artery facilitates clot lysis, assists in rapid and stable cerebrovascular
reperfusion, alleviates ischemic brain damage, and eliminates
mortality, whereas pretreatment with tPA is not protective even
at a 10-fold higher dose at which mortality is aggravated. At
protective doses, RBC/tPA did not consume plasma fibrinogen
or cause postsurgical bleeding or hemorrhage and toxicity in
the central nervous system in rodent models of brain ischemia
and thrombosis. These animal studies indicate that RBC/tPA might
provide thromboprophylaxis in patients at risk for cerebrovascular
thromboembolism in the postoperative period; after transient
ischemic attack, myocardial infarction, and stroke; or in the
setting of non–ST-elevation acute myocardial infarction,
which is characterized by multiple cycles of intravascular rethrombosis
and incomplete thrombolysis. Nascent and growing occlusive clots
represent the preferable target for RBC/tPA. Use of injectable
antithrombotic prodrugs conjugated with RBC binding peptides
may further enhance the clinical application of this new approach
toward prophylactic thrombolysis within the cerebral and other
vasculatures. See p
1442.
|
Activation of Liver X Receptors Promotes Neuroprotection and Reduces Brain Inflammation in Experimental Stroke
|
|---|
Liver X receptors (LXRs)
and β are ligand-activated transcription
factors that belong to the nuclear receptor superfamily. LXRs
regulate the expression of a number of genes involved in cholesterol
metabolism. In addition, LXRs are known to antagonize the expression
of a panel of inflammatory genes. All these pieces of evidence
suggest that LXR activation may exert a protective role in pathologies
in which inflammation is involved such as stroke. Taking into
account the epidemiological importance of stroke and the limited
possibilities for treatment, activation of LXR might arise as
a possible powerful approach for stroke treatment. The present
results demonstrate that the activation of the LXR receptors
exerts potent neuroprotective actions in experimental stroke,
which are concomitant to the inhibition of inflammatory mediators.
Apart from the possible therapeutic repercussions in acute stroke
management, these findings suggest, on one hand, that the endogenous
levels of LXR agonists such as oxysterols could serve as a helpful
prognostic marker in stroke patients and, on the other, that
polymorphisms or other alterations of the LXR receptor expression
or function may increase vulnerability to stroke. See p
1450.
|
Aortic Valve Bypass Surgery: Midterm Clinical Outcomes in a High-Risk Aortic Stenosis Population
|
|---|
Recent recognition that a large number of symptomatic patients
with aortic stenosis (AS) are not referred for surgery as a
result of real and perceived risks of conventional aortic valve
replacement has sparked interest in alternative therapies. Aortic
valve bypass (AVB; apicoaortic conduit) surgery relieves AS
by shunting blood from the apex of the left ventricle to the
descending thoracic aorta through a valved conduit. AVB surgery
has been performed, albeit uncommonly, for >45 years. The
aim of this study was to characterize outcomes in a series of
very high-risk AS patients treated with AVB surgery. A total
of 31 patients underwent AVB surgery. In all cases, the heart
was beating, and no ascending aortic manipulation was necessary.
Cardiopulmonary bypass was used briefly in 61% of patients and
has been used less commonly as experience has been gained in
performing AVB surgery on the beating heart. Echocardiographic
analyses demonstrated that AVB surgery was effective at relieving
the outflow obstruction associated with valvular AS, that blood
flow was predictably distributed between the conduit and native
left ventricular outflow tract, and that left ventricular performance
was preserved after surgery. Stroke and renal dysfunction were
uncommon after AVB surgery. This experience suggests that AVB
surgery is an important therapeutic option for the high-risk
AS patient. Continued improvements in technology and surgical
technique may warrant extending AVB surgery to moderate-risk
AS patients. See p
1460.
|
Inhibition of Stearoyl-Coenzyme A Desaturase 1 Dissociates Insulin Resistance and Obesity From Atherosclerosis
|
|---|
The metabolic syndrome has become a leading health concern in
developed countries. Importantly, the presence of the metabolic
syndrome has been shown to be a predictor of atherosclerotic
cardiovascular disease extent in humans. Simply by catalyzing
the conversion of long-chain saturated fatty acids to monounsaturated
fatty acids, stearoyl-coenzyme A desaturase 1 (SCD1) has been
shown to promote multiple aspects of the metabolic syndrome.
Therefore, inhibition of SCD1 is currently regarded as a promising
therapeutic strategy, yet little information exists on whether
SCD1 inhibition could also protect against atherosclerosis.
To examine this possibility, we inhibited SCD1 in a hyperlipidemic
mouse model of atherosclerosis. In agreement with previous reports,
inhibition of SCD1 protected against diet-induced obesity, insulin
resistance, hypertriglyceridemia, and hepatic steatosis. However,
quite unexpectedly, SCD1 inhibition strongly promoted aortic
atherosclerosis. Because dietary saturated fatty acids have
been shown to promote inflammation through toll-like receptor
4, we examined macrophage toll-like receptor 4 function. Interestingly,
SCD1 inhibition resulted in marked hypersensitivity to toll-like
receptor 4 agonists in macrophages. This study is the first
to report the consequences of inhibiting SCD1 on atherosclerosis.
Although the presence of the metabolic syndrome may be associated
with atherosclerosis in humans, this study provides evidence
that the metabolic syndrome can be completely dissociated from
atherosclerosis in mice. Taken together, these results suggest
that the link between obesity and systemic insulin resistance
and atherosclerosis should be approached with caution and that
SCD1 inhibition may not necessarily be a treatment for atherosclerosis
and its complications. See p
1467.
Related Articles:
-
Two-Year Survival and Mental and Psychomotor Outcomes After the Norwood Procedure: An Analysis of the Modified Blalock-Taussig Shunt and Right Ventricle–to–Pulmonary Artery Shunt Surgical Eras
- Joseph Atallah, Irina A. Dinu, Ari R. Joffe, Charlene M.T. Robertson, Reg S. Sauve, John D. Dyck, David B. Ross, Ivan M. Rebeyka, and the Western Canadian Complex Pediatric Therapies Follow-Up Group
Circulation 2008 118: 1410-1418.
[Abstract]
[Full Text]
-
Cerebrovascular Thromboprophylaxis in Mice by Erythrocyte-Coupled Tissue-Type Plasminogen Activator
- Kristina Danielyan, Kumkum Ganguly, Bi-Sen Ding, Dmitriy Atochin, Sergei Zaitsev, Juan-Carlos Murciano, Paul L. Huang, Scott E. Kasner, Douglas B. Cines, and Vladimir R. Muzykantov
Circulation 2008 118: 1442-1449.
[Abstract]
[Full Text]
-
Patent Foramen Ovale and Migraine: A Cross-Sectional Study From the Northern Manhattan Study (NOMAS)
- Tatjana Rundek, Mitchell S.V. Elkind, Marco R. Di Tullio, Emmanuel Carrera, Zhezhen Jin, Ralph L. Sacco, and Shunichi Homma
Circulation 2008 118: 1419-1424.
[Abstract]
[Full Text]
-
Pilot Trial on Determinants of Progenitor Cell Recruitment to the Infarcted Human Myocardium
- Volker Schächinger, Alexandra Aicher, Natascha Döbert, Rainer Röver, Jürgen Diener, Stephan Fichtlscherer, Birgit Assmus, Florian H. Seeger, Christian Menzel, Winfried Brenner, Stefanie Dimmeler, and Andreas M. Zeiher
Circulation 2008 118: 1425-1432.
[Abstract]
[Full Text]
-
Activation of Liver X Receptors Promotes Neuroprotection and Reduces Brain Inflammation in Experimental Stroke
- Jesús R. Morales, Iván Ballesteros, José Manuel Deniz, Olivia Hurtado, José Vivancos, Florentino Nombela, Ignacio Lizasoain, Antonio Castrillo, and María A. Moro
Circulation 2008 118: 1450-1459.
[Abstract]
[Full Text]
-
Transition From Chronic Compensated to Acute Decompensated Heart Failure: Pathophysiological Insights Obtained From Continuous Monitoring of Intracardiac Pressures
- Michael R. Zile, Tom D. Bennett, Martin St. John Sutton, Yong K. Cho, Philip B. Adamson, Mark F. Aaron, Juan M. Aranda, Jr, William T. Abraham, Frank W. Smart, Lynne Warner Stevenson, Fred J. Kueffer, and Robert C. Bourge
Circulation 2008 118: 1433-1441.
[Abstract]
[Full Text]
-
Aortic Valve Bypass Surgery: Midterm Clinical Outcomes in a High-Risk Aortic Stenosis Population
- James S. Gammie, Leandra S. Krowsoski, James M. Brown, Patrick N. Odonkor, Cindi A. Young, Mary J. Santos, John S. Gottdiener, and Bartley P. Griffith
Circulation 2008 118: 1460-1466.
[Abstract]
[Full Text]
-
Inhibition of Stearoyl-Coenzyme A Desaturase 1 Dissociates Insulin Resistance and Obesity From Atherosclerosis
- J. Mark Brown, Soonkyu Chung, Janet K. Sawyer, Chiara Degirolamo, Heather M. Alger, Tam Nguyen, Xuewei Zhu, My-Ngan Duong, Amanda L. Wibley, Ramesh Shah, Matthew A. Davis, Kathryn Kelley, Martha D. Wilson, Carol Kent, John S. Parks, and Lawrence L. Rudel
Circulation 2008 118: 1467-1475.
[Abstract]
[Full Text]
Top
Two-Year Survival and Mental...
Patent Foramen Ovale and...