Circulation. 2008;118:211-212
doi: 10.1161/CIRCULATIONAHA.108.189735
(Circulation. 2008;118:211-212.)
© 2008 American Heart Association, Inc.
Clinical Summaries
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Feasibility of Real-Time Magnetic Resonance Imaging for Catheter Guidance in Electrophysiology Studies
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Electrophysiology procedures provide a cure for many atrial
and ventricular arrhythmias but remain associated with failures
and complications, much of which likely derive from lack of
soft-tissue visualization with fluoroscopy. As an alternative
imaging modality, magnetic resonance imaging offers 3-dimensional
imaging with excellent soft-tissue resolution without the ionizing
radiation inherent to fluoroscopy. However, potential interactions
of static and gradient magnetic fields and radiofrequency energy
from the magnetic resonance scanner with the electrophysiology
system must be addressed for safe performance of real-time magnetic
resonance–guided electrophysiology procedures. In the
present study, we report the feasibility of performing electrophysiology
studies with a custom electrophysiology system compatible with
real-time magnetic resonance guidance. Successful anatomic targeting
of catheters was demonstrated, and comprehensive electrophysiology
studies with recording of intracardiac electrograms and pacing
were performed. The capabilities of magnetic resonance guidance
for superior real-time resolution of anatomic soft tissues,
identification of scar arrhythmia substrates, and monitoring
of lesion formation within linear sets and with respect to surrounding
structures may improve the safety and efficacy of complex electrophysiology
procedures. See p
223.
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Dietary Patterns and Risk of Mortality From Cardiovascular Disease, Cancer, and All Causes in a Prospective Cohort of Women
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Overall dietary patterns can be defined as combinations of characteristic
food groups that reflect existing eating habits of a specific
study population. The association between such overall dietary
patterns and mortality due to cardiovascular disease and other
chronic diseases is largely unknown. We followed a population
of >70 000 apparently healthy US women over the course of
18 years, assessing dietary intake repeatedly. By applying factor
analysis, we identified 2 major dietary patterns. A greater
adherence to the pattern labeled as
prudent (characterized by
a high consumption of plant foods such as vegetables, fruit,
legumes, and whole grains as well as fish and poultry) was related
to a 28% reduced risk of cardiovascular disease mortality and
a 17% reduced risk of premature all-cause mortality. By contrast,
a greater adherence to the pattern labeled as
western (characterized
by a high consumption of red and processed meat, refined grains,
french fries, and sweets) was associated with a 22% increased
risk of cardiovascular disease mortality, a 16% increased risk
of cancer mortality, and a 21% increased risk of premature all-cause
mortality. The observed associations were independent of known
risk factors including age, smoking, physical inactivity, body
mass index, and total caloric intake. Nutritional recommendations
to prevent chronic diseases and promote longevity may need to
focus on overall dietary patterns rather than individual nutrients.
See p
230.
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Transcriptomic Biomarkers for Individual Risk Assessment in New-Onset Heart Failure
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New technologies that measure expression levels of the entire
complement of messenger RNAs in a cell or tissue have become
highly useful for clinical prediction of disease origin, prognosis,
and therapeutic response. Because they are highly comprehensive,
they have the potential to be highly accurate. The present study
shows that this approach could be very important to fulfill
an unmet need in the field of heart failure: accurate prediction
of the long-term clinical course of a patient. New-onset heart
failure is very common and has a highly variable outcome; thus,
the ability to accurately assess individual patient risk is
of major significance. Using endomyocardial biopsy tissue obtained
at the time of clinical presentation, we developed a molecular
signature comprising 45 genes that predicted long-term clinical
outcome in patients with new-onset heart failure. This transcriptomic
biomarker distinguished patients who survived at least 5 years
after first diagnosis from those who did poorly and required
left ventricular mechanical assistance or cardiac transplantation
or who died. These findings may provide the physician with important
prognostic information about individual patients and could provide
tools for personalized treatment or monitoring. Importantly,
the biomarker can be obtained from a single endomyocardial biopsy
and therefore is clinically practical. The biomarker contained
biologically relevant genes, including those involved in regeneration
and angiopoiesis, which suggests possible novel therapeutic
targets. See p
238.
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Heritability and Genome-Wide Linkage in US and Australian Twins Identify Novel Genomic Regions Controlling Chromogranin A: Implications for Secretion and Blood Pressure
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Chromogranin A (CHGA) plays a necessary role in the formation
of catecholamine secretory granules, where it is cleaved to
catestatin, an inhibitor of catecholamine release. Catestatin
circulates in human plasma and may be an intermediate phenotype
in analysis of genetic risk for cardiovascular disease. In the
present investigation, we first observed that CHGA is elevated
and its processing to catestatin is diminished in hypertension.
To approach genetic control of catestatin in the population,
we used a human twin pair design. Studies of monozygotic and
dizygotic twins allow estimation of the contribution of genetic
variation to any trait (as heritability, or h
2), and dizygotic
or sibling pairs allow genome-wide approaches such as microsatellite
linkage scanning to identify previously unsuspected loci influencing
traits of interest. Our results indicate that the circulating
catestatin concentration has substantial heritability and that
novel genetic loci on chromosomes 4p, 4q, and 17q contribute
significantly to common interindividual variation in expression,
secretion, or enzymatic formation of this biologically active
peptide. At the
ATP6N1 (H
+-ATPase alpha subunit) positional
candidate locus on chromosome 17q, a common 3'-UTR variant predicted
plasma CHGA, CHGA-to-catestatin processing, and finally systolic
blood pressure in the population. Thus, ATP6N1 represents a
novel
trans-QTL for sympathochromaffin activity and ultimately
blood pressure. See p
247.
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Magnetic Resonance Imaging Contrast Agent Targeted Toward Activated Platelets Allows In Vivo Detection of Thrombosis and Monitoring of Thrombolysis
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Platelets play a pivotal role in thrombus formation and in the
development of atherosclerotic plaques from the very beginning
of atherosclerotic disease and particularly in the final stages
of plaque rupture and thrombotic vessel occlusion. Imaging of
platelets promises the sensitive detection of thrombi/emboli
and the identification of the role of platelets in the development
of atherosclerotic plaques. Detection of thrombi (eg, in coronary
and carotid arteries) and characterization of plaque stages
and the associated risk of vessel closure are of great clinical
interest. Recent magnetic resonance imaging (MRI) studies have
used microparticles of iron oxide (MPIOs), which cause intense
negative contrast effects in T2*-weighted MRI. Here, we describe
the generation and application of a targeted MRI contrast agent
consisting of MPIOs and a single-chain antibody that selectively
binds to ligand-induced binding sites (LIBS) on the activated
platelet integrin glycoprotein IIb/IIIa. We show the utility
of this contrast agent in the rapid identification of mural
platelet-containing thrombi in vivo using a mouse model of carotid
thrombosis. Pharmacological thrombolysis was used to demonstrate
that LIBS MPIO–induced signal void intensity reports reliably
on thrombus size, in particular on thrombus size reduction.
Furthermore, we applied LIBS MPIOs in symptomatic human eversion
endarterectomy specimens to show the detection of clinically
relevant platelet adhesion/aggregation in humans. In conclusion,
the described targeted MRI contrast agent represents a novel
and unique noninvasive imaging approach that allows the detection
and quantification of thrombi and can be used to monitor the
success or failure of thrombolytic therapy. See p
258.
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Comparison of Thrombolysis Followed by Broad Use of Percutaneous Coronary Intervention With Primary Percutaneous Coronary Intervention for ST-Segment–Elevation Acute Myocardial Infarction: Data From the French Registry on Acute ST-Elevation Myocardial Infarction (FAST-MI)
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Primary percutaneous coronary intervention (PCI) is the best
reperfusion method in patients with ST-elevation myocardial
infarction, provided it can be performed in a timely manner.
Because it remains difficult to implement on a large scale,
however, intravenous thrombolysis is still used in many patients.
This report presents data from a nationwide French registry
collecting consecutive patients over a 1-month period at the
end of 2005 and describes in-hospital and 1-year outcomes in
patients treated with primary PCI or intravenous thrombolysis
followed by routine coronary angiography in most patients (96%)
and a very high rate of secondary PCI (84%). As expected, intravenous
thrombolysis could be administered much more rapidly than primary
PCI, particularly because two thirds of the patients received
thrombolysis in the prehospital setting. There was no difference
in early and late mortality between patients with primary PCI
and those with a pharmacoinvasive strategy. One-year survival
was similar among 2 cohorts of patients matched on a propensity
score for receiving thrombolysis or primary PCI (93.8% and 93.3%).
Overall, this study shows that the combination of intravenous
thrombolysis with early PCI in patients seen in the first hours
after symptom onset yields clinical results that compare with
those of primary PCI. These findings may have important implications
for healthcare organizations. See p
268.
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Cardiovascular Risk Factors and the Metabolic Syndrome in Pediatric Nonalcoholic Fatty Liver Disease
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There are >10 million obese children in the United States.
Obese children differ in their risk for cardiovascular disease,
which may be underappreciated in part because specific comorbidities
are typically the focus of different disciplines such as cardiology,
endocrinology, gastroenterology, or nephrology. When working
with an obese child, one should consider how any single abnormality
may interact with another. Metabolic syndrome is a clustering
of risk factors for the development of cardiovascular disease
and type 2 diabetes mellitus. Nonalcoholic fatty liver disease
(NAFLD) is a common cause of chronic liver disease in children.
Both metabolic syndrome and NAFLD are associated with obesity.
We performed a case-control study in a large clinical sample
of overweight and obese children and adolescents with and without
NAFLD. NAFLD was strongly associated with metabolic syndrome.
The association was independent of both body mass index and
hyperinsulinemia. Thus, when one detects features of metabolic
syndrome in an obese child, one must be aware of the risk for
NAFLD. Similarly, the presence of NAFLD may serve to stratify
risk. The identification of NAFLD in a child should prompt consideration
of cardiovascular health. Global counseling should address nutrition,
physical activity, and avoidance of smoking. In an integrated
model of disease management, therapeutic goals for NAFLD should
include not only the prevention of end-stage liver disease but
also the prevention of cardiovascular disease and diabetes.
See p
277.
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Abrupt Shift of the Pattern of Diurnal Variation in Stroke Onset With Daylight Saving Time Transitions
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In the present study, we analyzed the influence of Daylight
Saving Time transitions on the circadian pattern of stroke onset
and identified abrupt shifts of stroke onset time points in
reference to the time effective before the transitions. Simply
put, after the transition into Daylight Saving Time, patients
appeared to have their strokes roughly 1 hour earlier than in
the weeks before, whereas the transition back from Daylight
Saving Time into standard time delayed stroke onset for
1 hour.
Our investigation suggests that the circadian profile of stroke
onset is coupled with the actual time of day. In modern civilizations,
the sleep-wake cycle is firmly synchronized with the actual
time of day, and clock change is likely to abruptly shift the
sleep-wake cycle of most individuals. Thus, the sleep-wake cycle
and factors associated with awakening (eg, the identification
of as yet unrecognized nighttime strokes) appear to be the most
important determinants of the diurnal pattern of stroke onset.
Conversely, it is well known that physiological parameters such
as blood pressure, platelet function, serum concentrations of
circulating hormones, and coagulation factors reveal a pattern
of diurnal rhythmicity that is governed by the molecular clock
and clock genes. However, the rapid shift of stroke onset time
points after Daylight Saving Time transitions does not support
the hypothesis that these endogenous factors play a major role
in determining the circadian profile of stroke onset, because
an entrainment of the human circadian clock within hours is
unlikely. See p
284.
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