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ABSTRACT: AimsEndothelial dysfunction is considered to play a key role in the development of atherosclerosis. However, only a limited number of human imaging studies have been available to demonstrate this hypothesis. The present study used near-infrared spectroscopy (NIRS) to investigate whether coronary endothelial dysfunction is associated with the lipid core plaque (LCP) in patients with early coronary artery disease.Methods and resultsA total of 32 patients with chest pain who had diameter stenosis <30% were enrolled. All patients underwent coronary endothelial function assessment using intracoronary acetylcholine infusion and NIRS of the proximal left anterior descending artery. The lipid core burden index (LCBI), LCBI/L (LCBI divided by the length of scanned artery), maxLCBI4 mm (maximum value of LCBI for any of the 4-mm segment) and block chemogram (yellow: probability of LCP presence >0.98, tan: 0.84 ≤ P ≤ 0.98, orange: 0.57 ≤ P ≤ 0.84, red: P < 0.57) were measured. The mean percentage of yellow, tan, and orange colour blocks in patients with epicardial endothelial dysfunction was significantly higher than in those with normal epicardial endothelial function (9.5 ± 11.4 vs. 3.1 ± 6.5%, P = 0.042). There was a significant correlation between LCBI (r = -0.460, P = 0.008), LCBI/L (r = -0.453, P = 0.009), and maxLCBI4 mm (r = -0.431, P = 0.014) and the degree of epicardial endothelial function. However, there was no significant correlation between LCBI (r = -0.101, P = 0.58), LCBI/L (r = -0.099, P = 0.59), and maxLCBI4 mm (r = -0.063, P = 0.73) and the degree of microvascular endothelial function.Conclusion
Patients with early coronary artery disease and endothelial dysfunction had a higher lipid content in the vascular wall than patients with normal endothelial function. The result of the present study supports the hypothesis that endothelial dysfunction is associated with pathogenesis of early atherosclerosis.
European Heart Journal 04/2013; · 10.48 Impact Factor
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Joerg Herrmann,
Ryan J Lennon, Gregory W Barsness,
Gurpreet S Sandhu,
Rajiv Gulati,
Patricia J M Best,
Paul Sorajja,
John F Bresnahan,
Verghese Mathew,
Malcolm R Bell,
Abhiram Prasad
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ABSTRACT: BACKGROUND: HIGH SENSITIVITY C-REACTIVE PROTEIN (HSCRP) HAS BEEN IDENTIFIED AS A PREDICTOR OF ADVERSE CARDIOVASCULAR OUTCOMES. WHETHER HSCRP IS A USEFUL BIOMARKER FOR RISK STRATIFICATION IN CONTEMPORARY PERCUTANEOUS CORONARY INTERVENTION REMAINS UNKNOWN.METHODS AND RESULTS: WE CONDUCTED A PROSPECTIVE STUDY AMONG 513 PATIENTS UNDERGOING NON-EMERGENCY PERCUTANEOUS CORONARY INTERVENTION AND EXAMINED THE RELATIONSHIP BETWEEN PRE- AND POSTPROCEDURAL HSCRP LEVELS AND OUTCOMES. THE PATIENTS WERE DIVIDED ACCORDING TO THE MEDIAN PREPROCEDURAL HSCRP LEVEL (0.3 MG/DL). PATIENTS WITH HIGH HSCRP HAD SIGNIFICANTLY MORE ADVERSE CLINICAL CHARACTERISTICS. PREPROCEDURAL HSCRP LEVEL WAS AN INDEPENDENT PREDICTOR OF PERIPROCEDURAL MYOCARDIAL INFARCTION (ODDS RATIO PER DOUBLING OF HSCRP 1.15 [95% CONFIDENCE INTERVAL, 1.011.31]; P=0.038). UNADJUSTED MORTALITY (29.7% VERSUS 9.9%; P0.001) AND THE COMBINED END POINT OF DEATH OR MYOCARDIAL INFARCTION (36.5% VERSUS 16.0%, P0.001) DURING A FOLLOW-UP OF 5 YEARS WERE MARKEDLY GREATER IN PATIENTS WITH HIGH PREPROCEDURAL HSCRP. SIMILAR RELATIONSHIPS EXISTED FOR POSTPROCEDURAL HSCRP. HOWEVER, AFTER MULTIVARIABLE ADJUSTMENT, NEITHER PREPROCEDURAL HSCRP LEVELS (HAZARD RATIO PER DOUBLING 0.96 [0.92, 1.00]; P=0.066) NOR POSTPROCEDURAL HSCRP LEVELS (HAZARD RATIO 0.98 [0.94, 1.02]; P=0.27) WERE SIGNIFICANTLY ASSOCIATED WITH MORTALITY.CONCLUSIONS: High hsCRP is associated with a greater independent risk of periprocedural myocardial infarction, as defined by the universal definition, but is not an independent determinant of mortality after percutaneous coronary intervention. Our findings suggest that routine measurement of hsCRP in patients undergoing percutaneous coronary intervention in contemporary practice is unlikely to be beneficial.
Circulation Cardiovascular Interventions 12/2012; · 6.06 Impact Factor
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Yoshiki Matsuo,
Takuro Takumi,
Verghese Mathew,
Woo-Young Chung, Gregory W Barsness,
Charanjit S Rihal,
Rajiv Gulati,
Eric T McCue,
David R Holmes,
Eric Eeckhout,
Ryan J Lennon,
Lilach O Lerman,
Amir Lerman
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ABSTRACT: Few studies have examined plaque characteristics among multiple arterial beds in vivo. The purpose of this study was to compare the plaque morphology and arterial remodeling between coronary and peripheral arteries using gray-scale and radiofrequency intravascular ultrasound (IVUS) at clinical presentation.
IVUS imaging was performed in 68 patients with coronary and 93 with peripheral artery lesions (29 carotid, 50 renal, and 14 iliac arteries). Plaques were classified as fibroatheroma (VH-FA) (further subclassified as thin-capped [VH-TCFA] and thick-capped [VH-ThCFA]), fibrocalcific plaque (VH-FC) and pathological intimal thickening (VH-PIT). Plaque rupture (13% of coronary, 7% of carotid, 6% of renal, and 7% of iliac arteries; P = NS) and VH-TCFA (37% of coronary, 24% of carotid, 16% of renal, and 7% of iliac arteries; P = 0.02) were observed in all arteries. Compared with coronary arteries, VH-FA was less frequently observed in renal (P < 0.001) and iliac arteries (P < 0.006). Lesions with positive remodeling demonstrated more characteristics of VH-FA in coronary (84% vs. 25%, P < 0.001), carotid (72% vs. 20%, P = 0.001), and renal arteries (42% vs. 4%, P = 0.001) compared with those with intermediate/negative remodeling. There was positive relationship between remodeling index and percent necrotic area in all four arteries.
Atherosclerotic plaque phenotypes were heterogeneous among four different arteries; renal and iliac arteries had more stable phenotypes compared with coronary artery. In contrast, the associations of remodeling pattern with plaque phenotype and composition were similar among the various arterial beds.
Atherosclerosis 05/2012; 223(2):365-71. · 3.79 Impact Factor
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Takuro Takumi,
Verghese Mathew, Gregory W Barsness,
Tetsuro Kataoka,
Ronen Rubinshtein,
Charanjit S Rihal,
Rajiv Gulati,
Eric Eeckhout,
Ryan J Lennon,
Lilach O Lerman,
Amir Lerman
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ABSTRACT: To evaluate the effect of plaque composition on renal function after renal artery intervention (RAI).
In 33 consecutive patients with atherosclerotic renal artery stenosis (enrolled between January 1, 2007, and April 30, 2009), renal angiography, pressure gradients across the lesion, and intravascular ultrasonography (IVUS) with virtual histology (VH)-derived plaque characteristics were assessed. In 25 patients who underwent RAI, estimated glomerular filtration rate (eGFR) was evaluated at baseline and at 3 months.
Mean pressure gradients across the lesion were poorly associated with baseline eGFR (r=-0.37; P=.07). In gray scale IVUS data, only remodeling index was significantly correlated with baseline eGFR (r=-0.38; P=.03). Plaque components classified by VH-IVUS had no correlation with baseline eGFR. During follow-up of 25 patients, the improvement in eGFR after RAI was observed in 9 patients, unchanged in 3, and deteriorated in 13. Overall, follow-up eGFR (median, 49.0 mL/min/1.73 m(2); interquartile range [IQR], 40.6-63.9 mL/min/1.73 m(2)) was unchanged compared with baseline eGFR (median, 53.8 mL/min/1.73 m(2); IQR, 41.4-63.4 mL/min/1.73 m(2); P=.38). The percent change in eGFR (median, -0.2%; IQR, -16.0% to 16.0%) after RAI had a significant negative correlation with the mean percentage of necrotic core classified by VH-IVUS (r=-0.47; P=.02), and the mean percentage of necrotic core was significantly larger in patients with deterioration of eGFR than in patients without deterioration of eGFR (median, 12.7%; IQR, 9.5%-19.5%; vs median, 8.3%; IQR, 5.5%-11.6%; P=.04).
In patients with atherosclerotic renal artery stenosis, the change in eGFR after RAI was related to plaque composition classified by VH-IVUS. The evaluation of plaque composition may provide more insights into the change in renal function after RAI.
Mayo Clinic Proceedings 12/2011; 86(12):1165-72. · 5.70 Impact Factor
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ABSTRACT: The left internal mammary artery (LIMA) is frequently utilized in coronary artery bypass grafting (CABG); adequate visualization of the LIMA bypass graft during diagnostic angiography is critical for determination of myocardial blood supply. We present a novel case of angiography via a left transradial approach demonstrating an occluded LIMA coronary bypass graft with antegrade flow maintained via a collateral branch from the ipsilateral thyrocervical trunk. Given the prevalence of LIMA use in CABG, it is critical to be aware of unusual configurations, including collateralization of a proximally occluded LIMA graft as described in this report.
The Journal of invasive cardiology 07/2011; 23(7):E181-2. · 1.84 Impact Factor
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Journal of vascular and interventional radiology: JVIR 05/2011; 22(5):730-2. · 1.81 Impact Factor
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ABSTRACT: We report a case of a thrombotic common iliac lesion with concern for elevated risk of downstream embolization during intervention. In this case, a transradial approach enabled the novel, simultaneous deployment of two embolic protection devices, one in the internal iliac artery and the other in the common femoral artery, for complete downstream protection during intervention. An endovascular stent, which accommodates a 0.035-inch wire lumen, was able to be delivered over both 0.014-inch protection device wires simultaneously and was successfully deployed with evidence of captured embolic material.
Journal of vascular surgery: official publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter 03/2011; 53(3):808-10. · 3.52 Impact Factor
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Circulation Cardiovascular Interventions 10/2009; 2(5):491-3. · 6.06 Impact Factor
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ABSTRACT: Endothelial dysfunction and atherosclerosis are systemic disorders, but are often characterised by segmental involvement and complications. A potential mechanism for local involvement early in the disease process may be related to plaque composition. This study was designed to test the hypothesis that in patients with minimal coronary atherosclerosis, coronary artery segments with abnormal endothelial function have specific plaque characteristics.
Intravascular ultrasound (IVUS) images were obtained from 30 patients who underwent coronary endothelial function assessment. Spectral analysis of the IVUS radiofrequency data was used for assessment of plaque composition. IVUS findings of the coronary sections were compared according to the corresponding endothelial response to acetylcholine.
Sections with a decrease epicardial coronary arterial diameter in response to acetylcholine had smaller baseline lumen (7.5 (2.4) mm(2) vs 8.8 (3.3) mm(2), p = 0.006) but larger plaque burden (37.1% (9.4%) vs 31% (7%), p = 0.003) than sections with normal endothelial response. Sections with endothelial dysfunction had larger necrotic core plaques: 0.13 (0.03-0.33) mm(2) vs 0.0 (0.0-0.07), p<0.001 and more dense calcium: 0.03 (IQR 0.0-0.13) mm(2) vs 0.0 (0.0-0.10) mm(2), p<0.01), than those with normal endothelial response. Only necrotic core area was associated with endothelial dysfunction (p<0.001) after adjusting for other measures.
This study suggests that local coronary endothelial dysfunction in patients with minimal coronary atherosclerosis is associated with plaque characteristics that are typical of vulnerable plaques.
Heart (British Cardiac Society) 07/2009; 95(18):1525-30. · 4.22 Impact Factor
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ABSTRACT: To present clinical outcomes with the use of embolic protection devices (EPDs) and renal artery stents in patients with chronic renal insufficiency (CRI) and renal artery stenosis (RAS).
A retrospective study was conducted in 23 patients with RAS and CRI who were treated with renal artery stent placement with an EPD. Follow-up data were obtained through medical records.
In 23 patients (18 men; 78%) with an average age of 69.4 years +/- 11 (range, 46-86 y), 32 renal arteries were treated for worsening renal function (n = 17; 74%) or uncontrolled hypertension and worsening renal function (n = 6; 26%). Nine FilterWire EZ devices were used in eight patients (35%) and 17 SpideRX devices were used in 15 patients (65%). The average follow-up was 8 months +/- 5. After the stent procedure, the mean systolic blood pressure decreased significantly (P < .05) whereas the diastolic pressure remained unchanged. There was a significant increase in the mean estimated glomerular filtration rate from 32.9 mL/min +/- 12.9 at baseline to 41.3 mL/min +/- 13.7 at last follow-up (P < .05). In 96% of patients, there was improvement or stabilization of kidney function. In six of the 17 SpideRX devices (35%), macroscopically evident embolic material was observed in the device after stent placement. There were two minor and two major complications.
Renal artery stent placement combined with the use of a SpideRX or FilterWire EZ device is associated with an good clinical outcome with a reasonable safety profile.
Journal of vascular and interventional radiology: JVIR 10/2008; 19(11):1639-45. · 1.81 Impact Factor
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ABSTRACT: To describe restenosis and clinical outcomes with drug-eluting stents (DESs) and compare them to those of bare metal stents (BMSs) in the treatment of symptomatic atherosclerotic renal artery stenosis (RAS) in the same patients.
A retrospective study was performed of all patients with RAS treated with a DES (Taxus Express 2 or Cypher). DESs were used for RASs with luminal vessel diameters of 4 mm or smaller and BMSs were used for those larger than 4 mm.
Sixteen patients (eight women; mean age, 72 years +/- 8) underwent treatment of 27 RASs for worsening renal function (n = 10) and uncontrolled hypertension (n = 6). Eighteen RASs were treated with 23 DESs (Cypher, n = 12; Taxus, n = 11) and nine were treated with BMSs. The average follow-up was 22 months +/- 10. After the procedure, the mean systolic blood pressure decreased significantly (P < .05), with no change in the mean diastolic pressure, serum creatinine, or number of antihypertensive medications. By Kaplan-Meier estimates, the 1- and 2-year patency rates for DESs were 78% and 68%, respectively; and for BMSs, the respective rates were 58% and 47% (P = NS). The average diameters of RASs were 3.4 mm +/- 0.6 in the DES group and 5.3 mm +/- 0.6 in the BMS group (P < .05). There were two technical failures (7.7%) in the DES group. There was one minor complication and a non-flow-limiting dissection.
DESs were used to treat RASs with good technical results and low restenosis rates compared with BMSs despite the smaller artery diameters in the DES group.
Journal of Vascular and Interventional Radiology 06/2008; 19(6):833-9. · 2.08 Impact Factor
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ABSTRACT: Women and men have different clinical presentations and outcomes in coronary artery disease (CAD). We tested the hypothesis that sex differences may influence coronary atherosclerotic burden and coronary endothelial function before development of obstructive CAD.
A total of 142 patients (53 men, 89 women; mean +/- SD age, 49.3 +/- 11.7 years) with early CAD simultaneously underwent intravascular ultrasonography and coronary endothelial function assessment. Atheroma burden in the left main and proximal left anterior descending (LAD) arteries was significantly greater in men than women (median, 23.0% vs. 14.1%, P = 0.002; median, 40.1% vs. 29.3%, P = 0.001, respectively). Atheroma eccentricity in the proximal LAD artery was significantly higher in men than women (median, 0.89 vs. 0.80, P = 0.04). The length of the coronary segments with endothelial dysfunction was significantly longer in men than women (median, 39.2 vs. 11.1 mm, P = 0.002). In contrast, maximal coronary flow reserve was significantly lower in women than men (2.80 vs. 3.30, P < 0.001). Sex was an independent predictor of atheroma burden in the left main and proximal LAD arteries (both P < 0.05) by multivariate analysis.
Men have greater atheroma burden, more eccentric atheroma, and more diffuse epicardial endothelial dysfunction than women. These results suggest that men have more severe structural and functional abnormalities in epicardial coronary arteries than women, even in patients with early atherosclerosis, which may result in the higher incidence rates of CAD and ST-segment myocardial infarction in men than women.
European Heart Journal 06/2008; 29(11):1359-69. · 10.48 Impact Factor
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ABSTRACT: The management of patients who suffer from medically refractory angina and are unsuitable for conventional revascularization therapy is often unsatisfactory. Enhanced external counterpulsation (EECP) is a noninvasive treatment that is safe and effective immediately after a course of treatment. However, the duration of benefit is less certain.
To evaluate the 3-year outcome of EECP treatment.
One thousand four hundred and twenty seven patients from 36 centers registered in the International EECP Patient Registry (IEPR)-Phase 1 was prospectively followed for a median of 37 months. Two hundred and twenty patients (15.4%) died, while 1,061 patients (74.4%) completed their follow-up.
The mean age was 66+/-11 years and 72% were men. Seventy-six percent had multivessel coronary disease for 11+/-8 years. Eighty-eight percent had a prior percutaneous or surgical revascularization and 82% were unsuitable for further coronary intervention. Immediately post-EECP, the proportion of patients with severe angina (Canadian Cardiovascular Angina Classification [CCS] III/IV) were reduced from 89% to 25%, p<0.001. The CCS class was improved by at least 1 class in 78% of the patients and by at least 2 classes in 38%. This was sustained in 74% of the patients during follow-up.Thirty-six percent of the patients had CCS II or less angina, which was better than pre-EECP state without a major adverse cardiovascular event during follow-up. More severe baseline angina and a history of heart failure or diabetes were independent predictors of unfavorable outcome.
An EECP improves angina and quality of life immediately after a course of treatment. For most of the patients, these beneficial effects are sustained for 3 years.
Clinical Cardiology 05/2008; 31(4):159-64. · 2.15 Impact Factor
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ABSTRACT: To test the hypothesis that allelic variants of the paraoxonase-1 gene are associated with endothelial dysfunction, an early stage of atherosclerosis.
We assessed 192Q>R and 55L>M allelic variants of the paraoxonase gene and coronary endothelial function in response to intracoronary acetylcholine in 99 patients (52 with homozygous QQ, 47 with homozygous RR or heterozygous QR). The study was conducted from September 1, 2002, through November 30, 2004.
Of 52 homozygous QQ patients, 39 (75%) had endothelial dysfunction vs 20 (43%) of the 47 RR/QR patients (P=.001), and this association remained significant after adjustment in a multivariable linear regression model (P=.005). In homozygous QQ vs RR/QR patients, epicardial arterial diameter decreased more (% change in diameter, -22%+/-21% vs -9%+/-16%, respectively, P=.002), coronary blood flow increased less (+37%+/-77% vs +75%+/-75%, P=.02) in response to acetylcholine, and oxidized LDL levels were higher. The 55L>M allelic variant was not significantly associated with endothelial dysfunction and had no effect on the association between endothelial dysfunction and the 192Q>R allelic variant.
The 192Q>R allelic variant of the paraoxonase-1 gene is associated with coronary endothelial dysfunction. The current study provides further information regarding the potential mechanisms by which this allelic variant contributes to early atherosclerosis in humans.
Mayo Clinic Proceedings 02/2008; 83(2):158-64. · 5.70 Impact Factor
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Journal of the American College of Cardiology 02/2008; 51(1):89-90. · 14.16 Impact Factor
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ABSTRACT: In recent years, improvements in both pharmacologic and revascularization therapies have greatly increased life expectancy for patients with coronary artery disease (CAD). As patients with more extensive CAD live longer, many develop myocardial ischemia and clinical angina that is not amenable to traditional revascularization therapy. Patients with severe, symptomatic, chronic CAD have been described as having refractory angina; they have also been termed "no-option" patients. This article discusses clinical management of this unique and growing group of patients and emerging therapeutic options including pharmacologic agents, enhanced external counterpulsation therapy, therapeutic angiogenesis, neurostimulation, and transmyocardial revascularization.
Minnesota medicine 02/2008; 91(1):36-9.
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ABSTRACT: In vitro and animal studies suggest that oxidative stress is associated with endothelial dysfunction. We tested whether local oxidative stress and nitric oxide (NO) bioavailability in the coronary circulation is associated with coronary endothelial dysfunction in humans. Blood samples were obtained simultaneously from the left main coronary artery and the coronary sinus for measurement of F2-isoprostanes, myeloperoxidase, nitrotyrosine, and superoxide dismutase in 20 patients without significant coronary disease. Afterward, coronary blood flow and the vascular response to intracoronary acetylcholine and NG-monomethyl-L-arginine (L-NMMA) were assessed. The gradient of isoprostanes between the arterial levels and coronary sinus correlated with the change in coronary artery diameter in response to acetylcholine (r=-0.79, P<0.0001). Isoprostanes net production across the left anterior descending artery territory correlated with a decrease in superoxide dismutase activity (r=0.66, P=0.002) and decrease in coronary artery diameter in response to L-NMMA (rs=0.48, P<0.05). Myeloperoxidase and nitrotyrosine gradients were similar in patients with endothelial dysfunction and controls. The effect of L-NMMA was similar in both groups. We conclude that coronary endothelial dysfunction in humans is characterized by local enhancement of oxidative stress without a decrease in basal NO release. This study supports the hypothesis that local oxidative stress has a role in reduction of NO bioavailability in humans with coronary endothelial dysfunction.
Hypertension 01/2008; 51(1):127-33. · 6.21 Impact Factor
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ABSTRACT: Over the past decade, the frequency of use of enhanced external counterpulsation (EECP) has increased in patients with angina, irrespective of medical therapy and coronary revascularization status. Many patients referred for EECP have one or more comorbidities that could affect this treatment's efficacy, safety, or both. By use of data from more than 8,000 patients enrolled in the International EECP Patient Registry, we provide practical guidelines for the selection and treatment of patients. We have focused on considerations for patients who have one or more of the following characteristics: age older than 75 years, diabetes, obesity, heart failure, and peripheral vascular disease. We have also reviewed outcomes and treatment recommendations for individuals with poor diastolic augmentation during treatment, for those with atrial fibrillation or pacemakers, and for those receiving anticoagulation therapy. Lastly, we examined relevant data regarding extended courses of EECP, repeat therapy, or both. While clinical studies have demonstrated the usefulness of EECP in selected patients, these guidelines permit recommendations for the extended application of this important treatment to subsets of patients excluded from clinical trials.
Nature Clinical Practice Cardiovascular Medicine 12/2006; 3(11):623-32. · 7.04 Impact Factor
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ABSTRACT: Modern coronary revascularization therapies, coronary artery bypass graft (CABG) surgery and percutaneous coronary intervention (PCI), continue to evolve and are widely applied. However, for patients with mild stable angina, or those who are asymptomatic with angiographically documented coronary artery disease (CAD), no survival benefit or reduction in the incidence of myocardial infarction has been demonstrated with CABG or PCI, except in the case of subgroups with angiographically determined high risk due to extensive multivessel disease with depressed LV function or left main CAD. At the same time, medical therapy continues to advance, with demonstrable benefit in both primary and secondary prevention of atherosclerotic coronary disease events. Patients with type 2 diabetes mellitus, at increased risk for adverse cardiac events, have been shown to benefit from these approaches as well. However, in asymptomatic or mildly symptomatic patients with documented ischemia and angiographically significant CAD, the incremental benefit-or hazard-associated with early revascularization superimposed on aggressive medical and risk factor modification therapies is unknown. We discuss the background and rationale for investigating the impact of early revascularization in patients with diabetes and CAD.
The American Journal of Cardiology 07/2006; 97(12A):31G-40G. · 3.37 Impact Factor
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ABSTRACT: Chronic refractory angina is a term used to describe patients who, despite optimal medical therapy, have both angina and objective evidence of ischaemia. It is estimated that 5-15% of the 12 million patients with chronic angina in the US meet the criteria for having refractory angina. This review focuses on the following evolving pharmacological therapies for chronic refractory angina: L-arginine, ivabradine, ranolazine, nicorandil and trimetazidine. Evolving devices and invasive procedures including enhanced external counterpulsation, spinal cord stimulation, and transmyocardial revascularisation are also briefly discussed.
Expert Opinion on Pharmacotherapy 03/2006; 7(3):259-66. · 3.20 Impact Factor
