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Konstantinos C Koskinas,
Galina K Sukhova,
Aaron B Baker,
Michail I Papafaklis,
Yiannis S Chatzizisis,
Ahmet U Coskun,
Thibaut Quillard,
Michael Jonas,
Charles Maynard,
Antonios P Antoniadis,
Guo-Ping Shi,
Peter Libby,
Elazer R Edelman,
Charles L Feldman, Peter H Stone
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ABSTRACT: OBJECTIVE: The mechanisms promoting the focal formation of rupture-prone coronary plaques in vivo remain incompletely understood. This study tested the hypothesis that coronary regions exposed to low endothelial shear stress (ESS) favor subsequent development of collagen-poor, thin-capped plaques. APPROACH AND RESULTS: Coronary angiography and 3-vessel intravascular ultrasound were serially performed at 5 consecutive time points in vivo in 5 diabetic, hypercholesterolemic pigs. ESS was calculated along the course of each artery with computational fluid dynamics at all 5 time points. At follow-up, 184 arterial segments with previously identified in vivo ESS underwent histopathologic analysis. Compared with other plaque types, eccentric thin-capped atheromata developed more in segments that experienced lower ESS during their evolution. Compared with lesions with higher preceding ESS, segments persistently exposed to low ESS (<1.2 Pa) exhibited reduced intimal smooth muscle cell content; marked intimal smooth muscle cell phenotypic modulation; attenuated procollagen-I gene expression; increased gene and protein expression of the interstitial collagenases matrix-metalloproteinase-1, -8, -13, and -14; increased collagenolytic activity; reduced collagen content; and marked thinning of the fibrous cap. CONCLUSIONS: Eccentric thin-capped atheromata, lesions particularly prone to rupture, form more frequently in coronary regions exposed to low ESS throughout their evolution. By promoting an imbalance of attenuated synthesis and augmented collagen breakdown, low ESS favors the focal evolution of early lesions toward plaques with reduced collagen content and thin fibrous caps-2 critical determinants of coronary plaque vulnerability.
Arteriosclerosis Thrombosis and Vascular Biology 05/2013; · 6.37 Impact Factor
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ABSTRACT: The heterogeneity of plaque formation, the vascular remodelling response to plaque formation, and the consequent phenotype of plaque instability attest to the extraordinarily complex pathobiology of plaque development and progression, culminating in different clinical coronary syndromes. Atherosclerotic plaques predominantly form in regions of low endothelial shear stress (ESS), whereas regions of moderate/physiological and high ESS are generally protected. Low ESS-induced compensatory expansive remodelling plays an important role in preserving lumen dimensions during plaque progression, but when the expansive remodelling becomes excessive promotes continued influx of lipids into the vessel wall, vulnerable plaque formation and potential precipitation of an acute coronary syndrome. Advanced plaques which start to encroach into the lumen experience high ESS at their most stenotic region, which appears to promote plaque destabilization. This review describes the role of ESS from early atherogenesis to early plaque formation, plaque progression to advanced high-risk stenotic or non-stenotic plaque, and plaque destabilization. The critical implication of the vascular remodelling response to plaque growth is also discussed. Current developments in technology to characterize local ESS and vascular remodelling in vivo may provide a rationale for innovative diagnostic and therapeutic strategies for coronary patients that aim to prevent clinical coronary syndromes.
Cardiovascular research 06/2012; 96(2):234-43. · 5.80 Impact Factor
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ABSTRACT: ST-segment elevation myocardial infarction (MI) is an emergency medical condition. Expediting the steps leading to coronary
reperfusion is of critical importance in improving survival after acute MI.
After the diagnosis of acute MI is made, patients should be treated with oxygen, aspirin, nitroglycerin, beta-blockers, heparin,
and analgesics, barring any contraindications.
If an experienced cardiac catheterization laboratory is available within 60 to 90 minutes, then catheter-based reperfusion
therapy is recommended; otherwise, thrombolysis should be considered as an alternate therapy.
Therapy with a reduced-dose thrombolytic agent and a glycoprotein IIb/IIIa receptor inhibitor appears to be of an added benefit
in establishing TIMI (Thrombolysis in Myocardial Infarction) 3 flow, but this approach awaits final approval prior to widespread
use.
The adjunctive use of glycoprotein IIb/IIIa receptor inhibitors with percutaneous transluminal coronary angioplasty, with
or without stenting, appears to be beneficial and is being used more frequently in the acute setting.
Coronary angiography should be performed in patients who fail to respond to thrombolytic therapy or who have evidence of recurrent
ischemia. This procedure should not be routinely performed in patients who have responded to thrombolytic therapy.
Four to 6 days after an acute MI event, assessment of left ventricular function is recommended. Submaximal exercise test (with
or without nuclear or echocardiographic imaging) should be considered in patients prior to discharge from the hospital—an
exception can be made in patients with one-vessel disease treated successfully with percutaneous transluminal coronary angioplasty.
After discharge, a regular exercise test should be obtained 4 to 6 weeks after an uncomplicated acute MI event.
Secondary prevention measures such as weight loss, cessation of smoking, aspirin, beta-blockers, lipid-lowering agents, and
angiotensin-converting enzyme inhibitors should be considered in all patients, barring contraindications.
Current Treatment Options in Cardiovascular Medicine 04/2012; 4(1):3-23.
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Journal of the American College of Cardiology 08/2011; 58(10):1083-1084. · 14.16 Impact Factor
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Peter H Stone
Journal of the American College of Cardiology 08/2011; 58(8):829-30. · 14.16 Impact Factor
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Circulation 08/2011; 124(7):763-5. · 14.74 Impact Factor
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ABSTRACT: Low endothelial shear stress (ESS) plays an important role in the progression and severity of atherosclerotic lesions. As 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) appear to stabilize plaque, it would be valuable to understand how statins affect the nature of lesions in the proatherogenic and proinflammatory environment of low ESS and the effect of statins on that atherosclerotic process. The purpose of this review is to summarize the relationship among low ESS, high-risk plaque and statins.
Low ESS is a critically important determinant of plaque development and progression to high-risk plaques with large necrotic lipid core, intensive inflammation and thin fibrous cap. In addition to the proatherogenic phenotypic switching in areas of low ESS, local LDL cholesterol concentrations are also increased in areas of low ESS, which exacerbates the local atherogenic process. In experimental models, statins appear to reduce the inflammation in lesions associated with low ESS and reduce the atherosclerotic phenotype even in these high-risk prone vascular areas.
The relationship between low ESS and statins has not been fully investigated, but the available data underscore the vasculoprotective effect of statins. Understanding the mechanisms whereby statins reduce the atherogenic and inflammatory phenotype resulting from a low ESS environment would provide new insights to design strategies to prevent regional formation of high-risk, inflamed plaques likely to rupture and cause an adverse clinical event.
Current opinion in lipidology 08/2011; 22(5):358-64. · 6.13 Impact Factor
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Yiannis S Chatzizisis,
Aaron B Baker,
Galina K Sukhova,
Konstantinos C Koskinas,
Michail I Papafaklis,
Roy Beigel,
Michael Jonas,
Ahmet U Coskun,
Benjamin V Stone,
Charles Maynard,
Guo-Ping Shi,
Peter Libby,
Charles L Feldman,
Elazer R Edelman, Peter H Stone
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ABSTRACT: Background- The molecular mechanisms that determine the localized formation of thin-capped atheromata in the coronary arteries remain unknown. This study tested the hypothesis that low endothelial shear stress augments the expression of matrix-degrading proteases and thereby promotes the formation of thin-capped atheromata. Methods and Results- Intravascular ultrasound-based, geometrically correct 3-dimensional reconstruction of the coronary arteries of 12 swine was performed in vivo 23 weeks after initiation of diabetes mellitus and a hyperlipidemic diet. Local endothelial shear stress was calculated in plaque-free subsegments of interest (n=142) with computational fluid dynamics. At week 30, the coronary arteries (n=31) were harvested and the same subsegments were identified. The messenger RNA and protein expression and elastolytic activity of selected elastases and their endogenous inhibitors were assessed. Subsegments with low preceding endothelial shear stress at week 23 showed reduced endothelial coverage, enhanced lipid accumulation, and intense infiltration of activated inflammatory cells at week 30. These lesions showed increased expression of messenger RNAs encoding matrix metalloproteinase-2, -9, and -12, and cathepsins K and S relative to their endogenous inhibitors and increased elastolytic activity. Expression of these enzymes correlated positively with the severity of internal elastic lamina fragmentation. Thin-capped atheromata developed in regions with lower preceding endothelial shear stress and had reduced endothelial coverage, intense lipid and inflammatory cell accumulation, enhanced messenger RNA expression and elastolytic activity of MMPs and cathepsins, and severe internal elastic lamina fragmentation. Conclusions- Low endothelial shear stress induces endothelial discontinuity and accumulation of activated inflammatory cells, thereby augmenting the expression and activity of elastases in the intima and shifting the balance with their inhibitors toward matrix breakdown. Our results provide new insight into the mechanisms of regional formation of plaques with thin fibrous caps.
Circulation 02/2011; 123(6):621-30. · 14.74 Impact Factor
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ABSTRACT: Permanent neurologic impairment following cardiac arrest is often severely debilitating, even after successful resuscitation. Therapeutic hypothermia decreases anoxic brain injury and subsequent cognitive deficits. Current practice guidelines recommend therapeutic hypothermia in comatose survivors of cardiac arrest. To address the multifacets of therapeutic hypothermia, we assembled a multidisciplinary task force including members from various specialties to create an evidence-based guideline with transparency across disciplines and consistency of care. We describe our institutional guidelines for the initiation and management of induced hypothermia in patients successfully resuscitated from a cardiac arrest.
Critical pathways in cardiology 12/2010; 9(4):216-20.
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11/2010; 3(11):1199-201. · 1.07 Impact Factor
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ABSTRACT: Atherosclerotic disease progression is determined by localized plaque growth, which is induced by systemic and local hemodynamic factors, and the nature of the wall remodeling response. The purpose of this review is to summarize the processes underlying the heterogeneity of coronary atherosclerosis progression in relation to the local hemodynamic and arterial remodeling environment.
Multiple competing biological processes in the extracellular matrix define the extent of vascular remodeling and disease progression. The remodeling phenomenon is not consistent but is characterized by great phenotypical heterogeneity which reflects the complex effect of systemic, genetic and hemodynamic factors on the arterial wall response to plaque formation and progression. The exaggeration of expansive remodeling (i.e., excessive expansive remodeling) likely contributes to the transformation of an initially favorable action into an excessive course of vessel expansion, continued disease progression and plaque instability. Extremely low endothelial shear stress and excessive expansive remodeling establish a vicious cycle which leads to the formation of severe plaques with high-risk characteristics.
The dynamic interplay between the local hemodynamic environment and the wall remodeling behavior determines the complexity of the natural history of atherosclerosis and explains the development of localized plaque vulnerability.
Current opinion in cardiology 11/2010; 25(6):627-38. · 2.66 Impact Factor
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ABSTRACT: The purpose of this explanatory analysis was to investigate the relationship between ST-segment depression and the rate-pressure product (RPP) during exercise to determine whether ranolazine's mechanism of action was related to a reduction in myocardial oxygen demand or preservation of myocardial oxygen supply.
In patients with stable ischemic heart disease, ranolazine increases exercise duration and reduces maximal ST-segment depression while exerting minimal effects on heart rate and blood pressure, although its mechanism of action during exercise has not been investigated.
Patients with stable ischemic heart disease (n = 191) were randomly allocated to a 4-period, double-blind, balanced Latin square crossover study to receive placebo, and ranolazine 500, 1,000, and 1,500 mg twice daily (bid) for 1 week each. Exercise treadmill tests were performed at baseline and at the end of each treatment period. The RPP and ST-segment depression were assessed before starting exercise, at each stage of exercise, and at maximal exercise.
Compared with placebo, ranolazine produced a dose-dependent reduction in ST-segment depression that became more marked as exercise-induced ischemia became more pronounced, associated with clinically minor decreases in heart rate and blood pressure. At 12-min exercise, the amount of ST-segment depression compared with placebo and controlled for RPP was reduced by 22.3% on ranolazine 500 mg bid (p = 0.137), by 35.4% on 1,000 mg bid (p = 0.005), and by 45.8% on 1,500 mg bid (p < 0.001).
The progressive magnitude of ischemia reduction on ranolazine was proportionally more substantial than the minor reductions in heart rate or RPP, suggesting that ranolazine's beneficial mechanism of action is most likely primarily due to an improvement in regional coronary blood flow in areas of myocardial ischemia.
Journal of the American College of Cardiology 09/2010; 56(12):934-42. · 14.16 Impact Factor
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ABSTRACT: Short-term elevation of ambient particulate air pollution has been associated with autonomic dysfunction and increased systemic inflammation, but the interconnections between these pathways are not well understood. We examined the association between inflammation and autonomic dysfunction and effect modification of inflammation on the association between air pollution and heart rate variability (HRV) in elderly subjects.
25 elderly subjects in Steubenville, Ohio, were followed up to 24 times with repeated 30-min ECG Holter monitoring (545 observations). C-reactive protein (CRP), fibrinogen, interleukin-6 (IL-6), soluble inter-cellular adhesion molecule 1 (sICAM-1), and white blood cell and platelet counts were measured in peripheral blood samples collected in the first month of the study. Increased systemic inflammation was defined for subjects within the upper 20% of the distribution for each marker. A central ambient monitoring station provided daily fine particle (PM(2.5)) and sulphate (SO(4)(2-)) data. Linear mixed models were used to identify associations between inflammatory markers and HRV and to assess effect modification of the association between air pollution and HRV due to inflammatory status.
A 5.8 mg/l elevation in CRP was associated with decreases of between -8% and -33% for time and frequency domain HRV outcomes. A 5.1 microg/m(3) increase in SO(4)(2-) on the day before the health assessment was associated with a decrease of -6.7% in the SD of normal RR intervals (SDNN) (95% CI -11.8% to -1.3%) in subjects with elevated CRP, but not in subjects with lower CRP (p value interaction=0.04), with similar findings for PM(2.5).
Increased systemic inflammation is associated with autonomic dysfunction in the elderly. Air pollution effects on reduced SDNN are stronger in subjects with elevated systemic inflammation.
Occupational and environmental medicine 09/2010; 67(9):625-30. · 3.64 Impact Factor
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Aaron B Baker,
Yiannis S Chatzizisis,
Roy Beigel,
Michael Jonas,
Benjamin V Stone,
Ahmet U Coskun,
Charles Maynard,
Campbell Rogers,
Konstantinos C Koskinas,
Charles L Feldman, Peter H Stone,
Elazer R Edelman
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ABSTRACT: Enzymatic degradation of the extracellular matrix is known to be powerful regulator of atherosclerosis. However, little is known about the enzymatic regulation of heparan sulfate proteoglycans (HSPGs) during the formation and progression of atherosclerotic plaques.
Swine were rendered diabetic through streptozotocin injection and hyperlipidemic through a high fat diet. Arterial remodeling and local endothelial shear stress (ESS) were assessed using intravascular ultrasound, coronary angiography and computational fluid dynamics at weeks 23 and 30. Coronary arteries were harvested and 142 arterial subsegments were analyzed using histomorphologic staining, immunostaining and real time PCR. Heparanase staining and activity was increased in arterial segments with low ESS, in lesions with thin cap fibroatheroma (TCFA) morphology and in lesions with severely degraded internal elastic laminae. In addition, heparanase staining co-localized with staining for CD45 and MMP-2 within atherosclerotic plaques. Dual staining with gelatinase zymography and heparanase immunohistochemical staining demonstrated co-localization of matrix metalloprotease activity with heparanase staining. A heparanase enzymatic activity assay demonstrated increased activity in TCFA lesions, subsegments with low ESS and in macrophages treated with oxidized LDL or angiotensin II.
Taken together, our results support a critical role for heparanase in the development of vulnerable plaques and suggest a novel therapeutic target for the treatment of atherosclerosis.
Atherosclerosis 09/2010; 213(2):436-42. · 3.79 Impact Factor
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ABSTRACT: The natural history of heterogeneous atherosclerotic plaques and the role of local hemodynamic factors throughout their development are unknown. We performed a serial study to assess the role of endothelial shear stress (ESS) and vascular remodeling in the natural history of coronary atherosclerosis.
Intravascular ultrasound-based 3-dimensional reconstruction of all major coronary arteries (n=15) was performed serially in vivo in 5 swine 4, 11, 16, 23, and 36 weeks after induction of diabetes mellitus and hyperlipidemia. The reconstructed arteries were divided into 3-mm-long segments (n=304). ESS was calculated in all segments at all time points through the use of computational fluid dynamics. Vascular remodeling was assessed at each time point in all segments containing significant plaque, defined as maximal intima-media thickness >/=0.5 mm, at week 36 (n=220). Plaque started to develop at week 11 and progressively advanced toward heterogeneous, multifocal lesions at all subsequent time points. Low ESS promoted the initiation and subsequent progression of plaques. The local remodeling response changed substantially over time and determined future plaque evolution. Excessive expansive remodeling developed in regions of very low ESS, further exacerbated the low ESS, and was associated with the most marked plaque progression. The combined assessment of ESS, remodeling, and plaque severity enabled the early identification of plaques that evolved to high-risk lesions at week 36.
The synergistic effect of local ESS and the remodeling response to plaque formation determine the natural history of individual lesions. Combined in vivo assessment of ESS and remodeling may predict the focal formation of high-risk coronary plaque.
Circulation 05/2010; 121(19):2092-101. · 14.74 Impact Factor
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ABSTRACT: Ambient particulate pollution and traffic have been linked to myocardial infarction and cardiac death risk. Possible mechanisms include autonomic cardiac dysfunction.
In a repeated-measures study of 46 patients 43-75 years of age, we investigated associations of central-site ambient particulate pollution, including black carbon (BC) (a marker for regional and local traffic), and report of traffic exposure with changes in half-hourly averaged heart rate variability (HRV), a marker of autonomic function measured by 24-hr Holter electrocardiogram monitoring. Each patient was observed up to four times within 1 year after a percutaneous intervention for myocardial infarction, acute coronary syndrome without infarction, or stable coronary artery disease (4,955 half-hour observations). For each half-hour period, diary data defined whether the patient was home or not home, or in traffic.
A decrease in high frequency (HF; an HRV marker of vagal tone) of 16.4% [95% confidence interval (CI), 20.7 to 11.8%] was associated with an interquartile range of 0.3-microg/m3 increase in prior 5-day averaged ambient BC. Decreases in HF were independently associated both with the previous 2-hr averaged BC (10.4%; 95% CI, 15.4 to 5.2%) and with being in traffic in the previous 2 hr (38.5%; 95% CI, 57.4 to 11.1%). We also observed independent responses for particulate air matter with aerodynamic diameter < or = 2.5 microm and for gases (ozone or nitrogen dioxide).
After hospitalization for coronary artery disease, both particulate pollution and being in traffic, a marker of stress and pollution, were associated with decreased HRV.
Environmental Health Perspectives 03/2010; 118(3):324-30. · 7.04 Impact Factor
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ABSTRACT: It is well recognized for that anatomic variations play a key role in the localization of atherosclerosis in the coronary
arterial system as well as in other susceptible arteries. Several decades of in vitro research as well as in vivo studies
in noncoronary arteries such as carotid arteries, first established that the factor responsible for local atherosclerosis
formation and progression was low endothelial shear stress (ESS), caused by irregularities in arterial geometry and the resulting
variations in local blood flow patterns.
Recent in vivo studies in humans and diabetic, hypercholesterolemic swine have shown unequivocally that low ESS promotes the
development of early fibroatheromas, which subsequently follow an individualized natural history of progression. This individual
natural history is critically dependent on the magnitude of low ESS, which subsequently regulates the severity of inflammation
within the wall and ultimately the vascular remodeling response. High-risk plaques develop in arterial areas with the lowest
values of ESS, which enhance plaque inflammation leading to excessive expansive remodeling. Excessive expansive remodeling
leads to perpetuation, or even exacerbation, of the local low ESS environment, thereby setting up a self-perpetuating vicious
cycle among low local ESS, inflammation, and excessive expansive remodeling, which transforms an early fibroatheroma to a
high-risk plaque. In view of this is seems reasonable to talk of vulnerable anatomy, with the understanding that local coronary anatomy is dynamic, ever changing with the growth and regression of individual
plaques and that the mediating factor, connecting anatomy to disease, is ESS.
Key wordsAtherosclerosis; Endothelial Shear Stress; Vulnerable Plaque; Periadventitial Fat; Pericardial Fat; Vascular Profiling; Intravascular
Ultrasound (IVUS)
12/2009: pages 495-506;
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ABSTRACT: Particulate pollution has been linked to risk for cardiac death; possible mechanisms include pollution-related increases in cardiac electrical instability. T-wave alternans (TWA) is a marker of cardiac electrical instability measured as differences in the magnitude between adjacent T waves. In a repeated-measures study of 48 patients aged 43 to 75 years, associations of ambient and home indoor particulate pollution, including black carbon (BC) and reports of traffic exposure, with changes in 0.5-hourly maximum TWA (TWA-MAX), measured by 24-hour Holter electrocardiographic monitoring, were investigated. Each patient was observed up to 4 times within 1 year after percutaneous intervention for myocardial infarction, acute coronary syndromes without infarction, or stable coronary artery disease, for a total of 5,830 0.5-hour observations. Diary data for each 0.5-hour period defined whether a patient was home or not home, or in traffic. Increases in TWA-MAX were independently associated with the previous 2-hour mean ambient BC (2.1%, 95% confidence interval 0.9% to 3.3%) and with being in traffic in the previous 2 hours (6.1%, 95% confidence interval 3.4% to 8.8%). When subjects were home, indoor home BC effects were largest and most precise; when subjects were away from home, ambient central site BC effects were strongest. Increases in pollution increased the odds of TWA-MAX > or =75th percentile (odds ratio 1.4, 95% confidence interval 1.2 to 1.6 for a 1 microg/m(3) increase in 6-hour mean BC). In conclusion, after hospitalization for coronary artery disease, being in traffic and short-term ambient or indoor BC exposure increased TWA, a marker of cardiac electrical instability.
The American journal of cardiology 09/2009; 104(5):665-70. · 3.58 Impact Factor
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ABSTRACT: In patients with unstable angina, evidence of myocardial ischemia on Holter monitoring is associated with an adverse prognosis. However, the association of duration and timing of ischemia on Holter monitoring with outcomes after percutaneous coronary intervention (PCI) in patients with non-ST-segment elevation acute coronary syndromes (NSTEACSs) has not been systematically evaluated. PROTECT-TIMI 30 randomized 857 patients with NSTEACSs undergoing PCI to eptifibatide plus a heparin product or bivalirudin monotherapy. Patients underwent continuous Holter monitoring following PCI, and the association between ischemia and clinical outcomes was evaluated retrospectively. Forty-three patients (5.0%) had ischemia on Holter after PCI. Any ischemia was associated with a significant increase in the incidence of death or myocardial infarction (MI) within 48 hours (32.6% vs 6.1%, odds ratio 7.5, 95% confidence interval 3.70 to 15.10, p <0.001). In patients who developed ischemia, there was a 1.44-fold increase in the odds for death or MI for every 30 minutes of ischemia (95% confidence interval 1.12 to 1.84, p = 0.004). Duration of ischemic events was related to their timing, such that ischemic events that occurred within the first 4 hours after PCI (median duration 141 minutes, interquartile range 36 to 227.5) were significantly longer than events occurring 4 to 24 hours after PCI (median duration 32.8 minutes, interquartile range 17.5 to 118, p = 0.041). In conclusion, early ischemia after PCI for NSTEACS is of longer duration, and longer duration of ischemia recognized by Holter monitoring is associated with an increased incidence of death or MI. Holter monitoring may be a useful surrogate end point in clinical trials.
The American journal of cardiology 08/2009; 104(1):36-40. · 3.58 Impact Factor
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ABSTRACT: The purpose of this study was to assess the relationship between ischemia detected on continuous electrocardiographic (cECG) recording and cardiovascular outcomes after acute coronary syndrome (ACS).
The small size of prior studies evaluating cECG prevented full evaluation of the risk associated with ischemia across subpopulations and compared with other methods of risk stratification. Ranolazine, a new antianginal agent, reduces ischemic symptoms in patients with chronic angina and after ACS but the anti-ischemic effect, as detected by cECG, is not known.
In all, 6,560 patients hospitalized with non-ST-segment elevation ACS were randomly assigned to ranolazine or placebo in the MERLIN-TIMI 36 (Metabolic Efficiency With Ranolazine for Less Ischemia in Non-ST-Elevation Acute Coronary Syndrome-Thrombolysis In Myocardial Infarction 36) trial. The cECG was performed for 7 days after randomization. Outcomes were followed for a median of 348 days. Clinical events that occurred during cECG recording were excluded from analysis.
A total of 6,355 (97%) patients had cECG recordings evaluable for ischemia analysis. Patients with >or=1 episode of ischemia on cECG (n = 1,271, 20%) were at increased risk of cardiovascular death (7.7% vs. 2.7%, p < 0.001), MI (9.4% vs. 5.0%, p < 0.001), and recurrent ischemia (17.5% vs. 12.3%, p < 0.001). The relationship with cardiovascular death was independent of baseline characteristics or elevated biomarkers (adjusted hazard ratio: 2.46, p < 0.001). Ischemia on cECG was associated with significantly worse outcomes in several subgroups. Ranolazine did not reduce the rate of ischemia detected on cECG (19.9% vs. 21.0%, hazard ratio: 0.93, p = 0.21).
In more than 6,300 patients with ACS, ischemia detected on cECG occurred frequently and was strongly and independently associated with poor cardiovascular outcomes, including cardiovascular death. Continuous ECG monitoring to detect ischemia after ACS may help to identify patients at increased risk. (Metabolic Efficiency With Ranolazine for Less Ischemia in Non-ST Elevation Acute Coronary Syndromes [MERLIN]; NCT00099788).
Journal of the American College of Cardiology 04/2009; 53(16):1411-21. · 14.16 Impact Factor
