Michael C. McDaniel

Coronary Artery Wall Shear Stress Is Associated With Progression and Transformation of Atherosclerotic Plaque and Arterial Remodeling in Patients With Coronary Artery Disease

Background Experimental studies suggest that low wall shear stress (WSS) promotes plaque development and high WSS is associated with plaque destabilization. We hypothesized that low-WSS segments in patients with coronary artery disease develop plaque progression and high-WSS segments develop necrotic core progression with fibrous tissue regression. Methods and Results Twenty patients with coronary artery disease underwent baseline and 6-month radiofrequency intravascular ultrasound (virtual histology intravascular ultrasound) and computational fluid dynamics modeling for WSS calculation. For each virtual histology intravascular ultrasound segment (n=2249), changes in plaque area, virtual histology intravascular ultrasound–derived plaque composition, and remodeling were compared in low-, intermediate-, and high-WSS categories. Compared with intermediate-WSS segments, low-WSS segments developed progression of plaque area (P=0.027) and necrotic core (P<0.001), whereas high-WSS segments had progression of necrotic core (P<0.001) and dense calcium (P<0.001) and regression of fibrous (P<0.001) and fibrofatty (P<0.001) tissue. Compared with intermediate-WSS segments, low-WSS segments demonstrated greater reduction in vessel (P<0.001) and lumen area (P<0.001), and high-WSS segments demonstrated an increase in vessel (P<0.001) and lumen (P<0.001) area. These changes resulted in a trend toward more constrictive remodeling in low- compared with high-WSS segments (73% versus 30%; P=0.06) and more excessive expansive remodeling in high- compared with low-WSS segments (42% versus 15%; P=0.16). Conclusions Compared with intermediate-WSS coronary segments, low-WSS segments develop greater plaque and necrotic core progression and constrictive remodeling, and high-WSS segments develop greater necrotic core and calcium progression, regression of fibrous and fibrofatty tissue, and excessive expansive remodeling, suggestive of transformation to a more vulnerable phenotype. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00576576.

Association of coronary wall shear stress with atherosclerotic plaque burden, composition, and distribution in patients with coronary artery disease.

Background Extremes of wall shear stress (WSS) have been associated with plaque progression and transformation, which has raised interest in the clinical assessment of WSS. We hypothesized that calculated coronary WSS is predicted only partially by luminal geometry and that WSS is related to plaque composition. Methods and Results Twenty‐seven patients with coronary artery disease underwent virtual histology intravascular ultrasound and Doppler velocity measurement for computational fluid dynamics modeling for WSS calculation in each virtual histology intravascular ultrasound segment (N=3581 segments). We assessed the association of WSS with plaque burden and distribution and with plaque composition. WSS remained relatively constant across the lower 3 quartiles of plaque burden (P=0.08) but increased in the highest quartile of plaque burden (P<0.001). Segments distal to lesions or within bifurcations were more likely to have low WSS (P<0.001). However, the majority of segments distal to lesions (80%) and within bifurcations (89%) did not exhibit low WSS. After adjustment for plaque burden, there was a negative association between WSS and percent necrotic core and calcium. For every 10 dynes/cm2 increase in WSS, percent necrotic core decreased by 17% (P=0.01), and percent dense calcium decreased by 17% (P<0.001). There was no significant association between WSS and percent of fibrous or fibrofatty plaque components (P=NS). Conclusions In patients with coronary artery disease: (1) Luminal geometry predicts calculated WSS only partially, which suggests that detailed computational techniques must be used to calculate WSS. (2) Low WSS is associated with plaque necrotic core and calcium, independent of plaque burden, which suggests a link between WSS and coronary plaque phenotype. (J Am Heart Assoc. 2012;1:e002543 doi: 10.1161/JAHA.112.002543.)

Coronary angiographic scoring systems: an evaluation of their equivalence and validity.

BACKGROUND Multiple scoring systems have been devised to quantify angiographic coronary artery disease (CAD) burden, but it is unclear how these scores relate to each other and which scores are most accurate. The aim of this study was to compare coronary angiographic scoring systems (1) with each other and (2) with intravascular ultrasound (IVUS)-derived plaque burden in a population undergoing angiographic evaluation for CAD. METHODS Coronary angiographic data from 3600 patients were scored using 10 commonly used angiographic scoring systems and interscore correlations were calculated. In a subset of 50 patients, plaque burden and plaque area in the left anterior descending coronary artery were quantified using IVUS and correlated with angiographic scores. RESULTS All angiographic scores correlated with each other (range for Spearman coefficient [ρ] 0.79-0.98, P < .0001); the 2 most widely used scores, Gensini and CASS-70, had a ρ = 0.90 (P < .0001). All scores correlated significantly with average plaque burden and plaque area by IVUS (range ρ 0.56-0.78, P < .0001 and 0.43-0.62, P < .01, respectively). The CASS-50 score had the strongest correlation (ρ 0.78 and 0.62, P < .0001) and the Duke Jeopardy score the weakest correlation (ρ 0.56 and 0.43, P < .01) with plaque burden and area, respectively. CONCLUSIONS Angiographic scoring systems are strongly correlated with each other and with atherosclerotic plaque burden. Scoring systems therefore appear to be a valid estimate of CAD plaque burden.

Contemporary Clinical Applications of Coronary Intravascular Ultrasound

Intravascular ultrasound (IVUS) provides valuable information on the coronary vascular lumen and wall and has been an important tool in the cardiac catheterization laboratory for over 2 decades. The major utility of IVUS relates to optimizing stent deployment, particularly in complex lesions. In percutaneous coronary intervention with bare-metal stents, IVUS guidance reduces restenosis. In percutaneous coronary intervention with drug-eluting stents, IVUS guidance may reduce rates of stent thrombosis with little affect on restenosis. The benefit of IVUS guidance is most important in complex lesion subsets, such as left main and bifurcation lesions, where studies suggest that IVUS guidance may reduce mortality. Whereas IVUS luminal area measurements have been used to assess intermediate lesion severity, recent studies have demonstrated that IVUS accurately identifies nonischemic lesions for which percutaneous coronary intervention can be safely deferred, but cannot accurately predict hemodynamically significant lesions and should not solely be used to justify revascularization. In the current review, we focus on clinical applications of IVUS in interventional cardiology.

Cardiac Arrest: A Treatment Algorithm for Emergent Invasive Cardiac Procedures in the Resuscitated Comatose Patient.

Patients who are comatose after cardiac arrest continue to be a challenge, with high mortality. Although there is an American College of Cardiology Foundation/American Heart Association Class I recommendation for performing immediate angiography and percutaneous coronary intervention (when indicated) in patients with ST-segment elevation myocardial infarction, no guidelines exist for patients without ST-segment elevation. Early introduction of mild therapeutic hypothermia is an established treatment goal. However, there are no established guidelines for risk stratification of patients for cardiac catheterization and possible percutaneous coronary intervention, particularly in patients who have unfavorable clinical features in whom procedures may be futile and affect public reporting of mortality. An algorithm is presented to improve the risk stratification of these severely ill patients with an emphasis on consultation and evaluation of patients prior to activation of the cardiac catheterization laboratory.

Myocardial bridging: contemporary understanding of pathophysiology with implications for diagnostic and therapeutic strategies.

Patients with myocardial bridging are often asymptomatic, but this anomaly may be associated with exertional angina, acute coronary syndromes, cardiac arrhythmias, syncope, or even sudden cardiac death. This review presents our understanding of the pathophysiology of myocardial bridging and describes prevailing diagnostic modalities and therapeutic options for this challenging clinical entity.

Combination of plaque burden, wall shear stress, and plaque phenotype has incremental value for prediction of coronary atherosclerotic plaque progression and vulnerability

AIMS Large plaque burden, certain phenotypes, and low wall shear stress (WSS) are associated with adverse outcomes and high WSS with development of plaque vulnerability. We aimed to investigate the incremental value of the combination of plaque burden, WSS and plaque phenotype for prediction of coronary atherosclerotic plaque progression and vulnerability. METHODS Twenty patients with CAD underwent baseline and 6-month follow-up coronary virtual histology-intravascular ultrasound (VH-IVUS) and computational fluid dynamics modeling for calculation of WSS. Low WSS was defined as <10 dynes/cm(2) and high WSS as ≥25 dynes/cm(2). Baseline plaque characteristics and WSS were related to plaque progression and vulnerability. RESULTS In 2249 VH-IVUS frames analyzed, coronary segments with both plaque burden >40% and low WSS had significantly greater change in plaque area at follow-up (+0.68 ± 1.05 mm(2)), compared to segments with plaque burden >40% without low WSS (-0.28 ± 1.32 mm(2)) or segments with low WSS and plaque burden ≤40% (+0.05 ± 0.71 mm(2)) (p = 0.047). Among plaque phenotypes, pathologic intimal thickening (PIT) had the greatest increase in necrotic core (NC) area (p = 0.06) and greatest decrease in fibro-fatty (FF) area (p < 0.0001). At follow-up, compared to segments with either plaque burden >60%, PIT, or high WSS, those with a combination of plaque burden >60%, PIT, and high WSS developed greater increase in NC area (p = 0.002), greater decrease in FF (p = 0.004) and fibrous areas (p < 0.0001), and higher frequency of expansive remodeling (p = 0.019). CONCLUSION Combination of plaque burden, WSS, and plaque phenotype has incremental value for prediction of coronary plaque progression and increased plaque vulnerability in patients with non-obstructive CAD.

Shear stress and plaque development

Although traditional cardiovascular risk factors ‘prime the soil’ for atherogenesis systemically, atherosclerosis primarily occurs in a site-specific manner with a predilection towards the inner wall of curvatures and outer wall of bifurcations with sparing of flow-dividers. Wall shear stress is a frictional force exerted parallel to the vessel wall that leads to alteration of the endothelial phenotype, endothelial cell signaling, gene and protein expression leading to a proinflammatory phenotype, reduced nitric oxide availability and disruption of the extracellular matrix, which in turn leads to plaque development. Clinical and experimental data are emerging that suggest the pathobiology associated with abnormal wall shear stress results in atherosclerotic plaque development and progression.

The role of plasma aminothiols in the prediction of coronary microvascular dysfunction and plaque vulnerability

BACKGROUND Although oxidative stress is considered a key pathogenic step in mediating vascular dysfunction and atherosclerosis development, their association has not been evaluated in human coronary circulation in vivo. Accordingly, we hypothesized that higher oxidative stress would be associated with abnormal coronary epicardial structure and microvascular function. METHODS We measured coronary flow velocity reserve (CFVR) and hyperemic microvascular resistance (HMR) as indices of microvascular function, and epicardial plaque volume and necrotic core using intravascular ultrasound (IVUS) in 47 patients undergoing cardiac catheterization. Plasma glutathione, cystine and their ratio served as measures of oxidative stress while high-sensitivity C-reactive protein (hs-CRP) served as a measure of inflammation. RESULTS Lower glutathione, a measure of increased oxidative stress was associated with impaired microvascular function [CFVR (r=0.39, p=0.01) and HMR (r=-0.43, p=0.004)], greater plaque burden (r=-0.32, p=0.03) and necrotic core (r=-0.39, p=0.008). Similarly, higher cystine/glutathione ratio was associated with impaired microvascular function [CFVR (r=-0.29, p=0.04)] and greater necrotic core (r=0.37, p=0.01). In comparison, higher hs-CRP was associated only with greater necrotic core (r=0.45, p=0.003). After multivariate adjustment for age, gender, hypertension, diabetes, acute coronary syndrome presentation, body mass index, tobacco abuse, statin use and hs-CRP, glutathione remained an independent predictor of CFVR, HMR and necrotic core (p<0.05). CONCLUSIONS Lower plasma glutathione level a measure of increased oxidative stress, was an independent predictor of impaired coronary microvascular function and plaque necrotic core.

Baseline fractional flow reserve and stent diameter predict optimal post-stent fractional flow reserve and major adverse cardiac events after bare-metal stent deployment.

OBJECTIVES We sought to identify baseline clinical, angiographic, and hemodynamic variables associated with optimal bare-metal stent (BMS) deployment, allowing selection of patients for treatment with BMS. BACKGROUND Patients with fractional flow reserve (FFR) >0.90 after BMS have low (<6%) major adverse cardiac event rates (MACE). We hypothesized that baseline variables can predict post-stent FFR >0.90 and MACE after BMS. METHODS In 586 patients from the multicenter post-BMS FFR registry, we developed multivariable logistic regression models to identify clinical, angiographic, and hemodynamic variables associated with post-stent FFR >or=0.90 and 6-month MACE. RESULTS After adjusting for potential confounders, baseline FFR (odds ratio [OR]: 5.0) and stent diameter (OR: 2.5 per millimeter) were predictive of post-stent FFR >0.90. Lower FFR (OR: 7.8); smaller stent diameter (OR: 3.7 per millimeter); longer stent length (OR: 1.0 per millimeter); and larger minimal luminal diameter (OR: 2.2 per millimeter) were predictors of MACE. In patients receiving 3-mm diameter stents, baseline FFR >0.70 yielded significantly higher likelihood of achieving post-stent FFR >0.90 than baseline FFR <or=0.70 (77% vs. 63%, p < 0.05); and in patients receiving <3-mm diameter stents, baseline FFR <0.50 was associated with higher MACE than FFR 0.50 to 0.70, and FFR >0.70 (40% vs. 15% vs. 13%, p < 0.05). CONCLUSIONS In patients receiving BMS, baseline FFR and stent diameter are predictors of post-stent FFR >0.90; and baseline FFR, stent diameter, stent length, and minimal luminal diameter are predictors of MACE. These variables may allow selection of patients who will have excellent results with BMS.