Circulation. 2009;119:3163-3164
doi: 10.1161/CIRCULATIONAHA.109.192192
(Circulation. 2009;119:3163-3164.)
© 2009 American Heart Association, Inc.
Clinical Summaries
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Dynamic Interactions Between Musical, Cardiovascular, and Cerebral Rhythms in Humans
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Music therapy is increasingly used in different disciplines,
from neurological disease to exercise training; its physiological
basis is not well understood, even in normal subjects. We therefore
studied responses in young normal subjects (12 practicing musicians
and 12 control subjects) to short tracks (in random order) from
opera (Puccini, Verdi), a cantata (Bach), and an orchestral
piece (Beethoven). We show (counterintuitively) that the structure
of a piece of music has a constant dynamic influence on cardiovascular
and respiratory responses, which correlate with music profiles.
This continuous "mirroring" of music profiles appears to be
present in all subjects, regardless of musical training, practice,
or personal taste, even in the absence of accompanying emotion.
Moreover, we found that some music (particularly by Verdi) has
phrasing with similar rhythm (6 cycles/min) to the spontaneous
waves in blood pressure (Mayer waves) and other circulatory
variables. This entrains spontaneous cardiovascular fluctuations
to the music rhythm and modifies cardiovascular control. These
findings contrast with the common belief that music appreciation
is personal and that cardiovascular reactions to music are secondary
to emotional responses. Our findings suggest that music is sensed
and processed at a subconscious level, closely mirrored by autonomic
cardiovascular responses. These results have clear implications
for the practice of music therapy: If music induces similar
physiological effects in different subjects, standard therapeutic
interventions should be possible. Furthermore, the present findings
help advance our understanding of how music can transmit emotions
and how music could be used to induce or enhance specific cardiovascular
responses in various fields, from physical training to recovery
from stroke. See p
3171.
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Soluble CXCL16 Predicts Long-Term Mortality in Acute Coronary Syndromes
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CXCL16/SR-PSOX is an interferon-
–regulated chemokine involved
in inflammation, lipid metabolism, and matrix degradation. Enhanced
expression of CXCL16 has been found in atherosclerotic lesions.
On the basis of its potential proatherogenic properties as well
as the ability of soluble CXCL16 to reflect upstream inflammation,
we hypothesized that soluble CXCL16 concentrations are associated
with long-term outcome in patients with acute coronary syndromes.
In a large group of patients with acute coronary syndromes,
we found that the CXCL16 level during the initial 24 hours of
admission predicted long-term mortality. This was the case even
when accounting for a number of clinical variables, in addition
to troponin T, C-reactive protein, pro–B-type natriuretic
peptide, and ejection fraction. Rehospitalization for an acute
myocardial infarction or congestive heart failure was also predicted
by CXCL16 level, even when adjusting for clinical variables.
Our findings suggest that CXCL16 should be further investigated
as a potential risk marker in even larger populations of patients
with coronary artery disease, as well as in those at risk for
development of such disorders. Although we found a strong association
between CXCL16 and total mortality, recommendations for implementing
CXCL16 measurements in acute coronary syndromes must await further
studies in larger patient populations, testing the prognostic
value of a model consisting of conventional risk markers and
CXCL16. See p
3181.
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Importance of Treadmill Exercise Time as an Initial Prognostic Screening Tool in Patients With Systolic Left Ventricular Dysfunction
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Physicians often refer patients with advanced heart failure
for exercise testing with metabolic gas exchange measurements
to assess suitability for cardiac transplantation. Peak oxygen
consumption and other metabolic measures are known to be powerful
predictors of mortality. We asked whether treadmill exercise
time according to a standardized protocol might be comparable
to peak oxygen consumption for assessment of prognosis. We analyzed
the outcomes of 2231 patients with systolic heart failure who
all underwent metabolic exercise stress testing on a modified
Naughton protocol. During a mean follow-up of 5 years, 742 patients
(33%) died, and 249 patients (11%) underwent heart transplantation
urgently. We found that after accounting for baseline clinical
characteristics, treadmill exercise time performed similarly
to peak oxygen consumption for predicting poor outcome. For
a 1-minute change in exercise time, there was a 7% increased
hazard of death (eg, comparing 480 to 540 seconds, hazard ratio
=1.07, 95% confidence interval 1.02 to 1.12,
P=0.004). Mortality
rates were particularly high for women who exercised less than
5 minutes and 17 seconds and for men who exercised less than
6 minutes. Our findings suggest that treadmill exercise time
may be valuable as an initial prognostic screening tool in patients
with advanced heart failure. See p
3189.
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Safety and Efficacy of Drug-Eluting and Bare Metal Stents: Comprehensive Meta-Analysis of Randomized Trials and Observational Studies
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Drug-eluting stents (DES) are currently implanted in the majority
of the >2 million patients undergoing percutaneous coronary
intervention each year. The evidence base for initial DES approvals
by the US Food and Drug Administration has consisted largely
of randomized controlled trials enrolling patients with relatively
noncomplex lesions. Data from these trials have suggested that
rates of death and myocardial infarction are similar among DES-
and bare metal stent–treated patients. Yet, DES are currently
being used "off label" in the majority of cases, and concerns
have arisen about the appropriateness of the use of DES in the
"real world." Here, we sought to address DES safety and efficacy
by synthesizing studies of the commercially available formulations
of the 2 originally approved DES. A statistical methodology
known as meta-analysis was used to quantitatively combine these
studies. Given the inherent differences between randomized controlled
trials and observational studies, each type of study was analyzed
separately. In randomized controlled trials, no significant
differences were observed in the long-term rates of either death
or myocardial infarction after DES or bare metal stent use for
both off-label and on-label indications. In nonrandomized observational
studies, DES use was associated with reduced death and myocardial
infarction. Both randomized controlled trials and observational
studies demonstrated marked and comparable reductions in repeat
revascularization with DES compared with bare metal stents.
In aggregate, the unrestricted use of DES compared with bare
metal stents did not appear to be associated with adverse safety
outcomes and was associated with a significant reduction in
repeat revascularization of the treated vessel. See p
3198.
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Triple Versus Dual Antiplatelet Therapy in Patients With Acute ST-Segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention
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Drug-eluting stent implantation in acute myocardial infarction
is associated with an increased risk for acute and subacute
in-stent thrombosis. Increased platelet activity also has been
observed in acute myocardial infarction. Therefore, more aggressive
antiplatelet therapy rather than conventional dual antiplatelet
therapy may offer extra benefits for acute myocardial infarction
patients undergoing primary percutaneous coronary intervention
with drug-eluting stents. This article retrospectively evaluates
the safety and efficacy of triple antiplatelet therapy (aspirin
plus clopidogrel plus cilostazol; n=1634) and dual antiplatelet
therapy (aspirin plus clopidogrel; n=2569) in 4203 ST-segment
elevation myocardial infarction patients who underwent primary
percutaneous coronary intervention with drug-eluting stents.
Selection of patients for treatment with triple antiplatelet
therapy was left to the physician’s discretion. Compared
with dual antiplatelet therapy, triple antiplatelet therapy
had a similar incidence of major bleeding events but a significantly
lower incidence of in-hospital mortality. After adjustment for
known confounders, triple antiplatelet therapy had significantly
lower incidences of cardiac death (adjusted odds ratio, 0.52;
95% confidence interval, 0.32 to 0.84;
P=0.007), total death
(adjusted odds ratio, 0.60; 95% confidence interval, 0.41 to
0.89;
P=0.010), and total major adverse cardiac events (adjusted
odds ratio, 0.74; 95% confidence interval, 0.58 to 0.95;
P=0.019)
at 8 months than dual antiplatelet therapy. In this large, real-world
clinical study in patients with ST-segment elevation myocardial
infarction who underwent primary percutaneous coronary intervention
with drug-eluting stents, triple antiplatelet therapy not only
had a good safety profile but also improved midterm clinical
outcomes. Randomized trials are needed to compare the safety
and efficacy of the triple and dual antiplatelet therapies in
these patients. See p
3207.
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Intensifying Platelet Inhibition With Tirofiban in Poor Responders to Aspirin, Clopidogrel, or Both Agents Undergoing Elective Coronary Intervention: Results From the Double-Blind, Prospective, Randomized Tailoring Treatment With Tirofiban in Patients Showing Resistance to Aspirin and/or Resistance to Clopidogrel Study
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Previous studies have shown that individual response to aspirin
or clopidogrel intake may vary significantly among patients,
and those who respond less have been reported to be at higher
risk for worse cardiovascular outcomes, especially if treated
with percutaneous coronary intervention. It is unknown whether
this worse cardiovascular outcome directly reflects suboptimal
platelet inhibition per se, which might benefit from more potent
antiplatelet agents. Alternatively, this may simply represent
a "marker" of worse prognosis without clear therapeutic implications.
In this study, we have shown that intensifying platelet inhibition
through the use of tirofiban, a potent intravenous antiplatelet
agent, in patients undergoing percutaneous coronary intervention
who have previously been selected to be poor responders to aspirin,
clopidogrel, or both agents leads to lower incidence of periprocedural
myocardial infarction compared with standard care consisting
of aspirin and clopidogrel. Thus, data are provided for the
first time showing that implementing alterative treatment strategies
in this patient population may result in an improved outcome
compared with standard care. Our results may suggest a causal
relationship between suboptimal platelet inhibition and worse
outcomes in this selected patient population. See p
3215.
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ATP-Binding Cassette Transporter A1 Expression and Apolipoprotein A-I Binding Are Impaired in Intima-Type Arterial Smooth Muscle Cells
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Arterial smooth muscle cells (SMCs) are a major cellular component
of atherosclerotic lesions and, like macrophages, accumulate
excess cholesterol. This study provides evidence that expression
of the major mediator of cholesterol removal from cells and
the rate-limiting protein in new high-density lipoprotein particle
formation, ATP-binding cassette transporter A1 (ABCA1), is reduced
in intima-type cultured SMCs, in human coronary atherosclerotic
intima, and specifically in atherosclerotic intimal SMCs. Remarkably,
overexpression of ABCA1 in cultured intima-type SMCs failed
to correct the binding of the main protein of high-density lipoprotein,
apolipoprotein A-I, to the cells or cholesterol efflux from
these cells. These results provide a previously unknown explanation
for the accumulation of excess cholesterol in intimal smooth
muscle foam cells and suggest that differences in gene and protein
expression by medial and intimal SMCs might identify apolipoprotein
A-I binding factors required for new high-density lipoprotein
particle formation. Identification of these factors would provide
novel targets for raising high-density lipoprotein clinically
for the prevention of atherosclerosis. See p
3223.
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