Ryan D. Madder

Detection by Near-Infrared Spectroscopy of Large Lipid Core Plaques at Culprit Sites in Patients With Acute ST-Segment Elevation Myocardial Infarction

OBJECTIVES This study sought to describe near-infrared spectroscopy (NIRS) findings of culprit lesions in ST-segment elevation myocardial infarction (STEMI). BACKGROUND Although autopsy studies demonstrate that most STEMI are caused by rupture of pre-existing lipid core plaque (LCP), it has not been possible to identify LCP in vivo. A novel intracoronary NIRS catheter has made it possible to detect LCP in patients. METHODS We performed NIRS within the culprit vessels of 20 patients with acute STEMI and compared the STEMI culprit findings to findings in nonculprit segments of the artery and to findings in autopsy control segments. Culprit and control segments were analyzed for the maximum lipid core burden index in a 4-mm length of artery (maxLCBI(4mm)). RESULTS MaxLCBI(4mm) was 5.8-fold higher in STEMI culprit segments than in 87 nonculprit segments of the STEMI culprit vessel (median [interquartile range (IQR)]: 523 [445 to 821] vs. 90 [6 to 265]; p < 0.001) and 87-fold higher than in 279 coronary autopsy segments free of large LCP by histology (median [IQR]: 523 [445 to 821] vs. 6 [0 to 88]; p < 0.001).Within the STEMI culprit artery, NIRS accurately distinguished culprit from nonculprit segments (receiver-operating characteristic analysis area under the curve = 0.90). A threshold of maxLCBI(4mm) >400 distinguished STEMI culprit segments from specimens free of large LCP by histology (sensitivity: 85%, specificity: 98%). CONCLUSIONS The present study has demonstrated in vivo that a maxLCBI(4mm) >400, as detected by NIRS, is a signature of plaques causing STEMI.

Composition of Target Lesions by Near-Infrared Spectroscopy in Patients With Acute Coronary Syndrome Versus Stable Angina

Background— Whereas acute coronary syndromes (ACS) typically develop from the rupture of lipid core plaque (LCP), lesions causing stable angina are believed to be composed of fibrocalcific plaque. In this study, intracoronary near-infrared spectroscopy (NIRS) was used to determine the frequency of LCP at target and remote sites in patients with ACS versus those with stable angina. Methods and Results— The study was performed in patients having ≥1 target lesion identified by invasive angiography who also underwent NIRS before intervention. LCP was defined as a 2-mm segment on the NIRS block chemogram having a strong positive reading indicated by a bright-yellow color. Patients with ACS and those with stable angina were compared for the frequency of LCP at target and remote sites. Among 60 patients (46.7% with ACS) undergoing invasive angiography and NIRS, 68 target lesions were identified. Although target lesions in patients with ACS were more frequently composed of LCP than targets in patients with stable angina (84.4% versus 52.8%, P=0.004), approximately one half of target lesions in patients with stable angina contained LCP. LCPs anatomically remote from the target lesion were frequent in patients with ACS and less common in patients with stable angina (73.3% versus 17.6%, P=0.002). Conclusions— Target lesions responsible for ACS were frequently composed of LCP; in addition, LCPs often were found in remote, nontarget areas. Both target and remote LCPs were more common in patients with ACS than in those with stable angina. Approximately one half of target lesions in stable patients were also composed of LCP.

Refining the Approach to Renal Artery Revascularization

Renal artery stenosis (RAS) is caused by a heterogenous group of diseases with different pathophysiology, clinical manifestations, treatment approaches, and outcomes. The 2 most common forms of RAS are fibromuscular dysplasia (FMD) and atherosclerosis (ARAS). Renovascular syndromes are broadly classified into renovascular hypertension and ischemic nephropathy, but these terms are misleading, because they imply a causal relationship between RAS, hypertension, and renal dysfunction, which is difficult to prove in humans. Data supporting renal revascularization are limited by heterogeneous causes of hypertension and renal dysfunction, insufficient understanding of the relationship between RAS and nephropathy, inconsistent techniques for revascularization, ambiguous terminology and end points to assess benefit, and lack of large-scale randomized trials. The purpose of this review is to enhance understanding of the epidemiology, clinical markers, and diagnosis of RAS; the relationship between RAS and important disease states; the distinction between renal ischemia and nephropathy; optimal revascularization techniques; and avoidance of renal injury.

Features of Disrupted Plaques by Coronary Computed Tomographic Angiography Correlates With Invasively Proven Complex Lesions

Background—This study was designed as a “proof-of-concept” to establish whether coronary computed tomographic angiography (CTA) has the capability to identify morphological features of plaque disruption. Methods and Results—In patients with unstable angina undergoing CTA and invasive coronary angiography within 30 days, quantitative CTA analysis was performed on all plaques for percent stenosis, volume, remodeling index, and volume of low-attenuation plaque (<50 Hounsfield units). Plaques with >25% stenosis were evaluated for CTA features of disruption, including ulceration and intraplaque dye penetration. Using invasive coronary angiography complex plaque as the reference standard for disruption, the sensitivity and specificity of ulceration and intraplaque dye penetration by CTA were determined. In 60 patients, 294 plaques were identified by CTA, of which 109 (37%) had features of disruption, including ulceration in 53 (18%) lesions and intraplaque dye penetration in 80 (27%). Compared with nondisrupted lesions, plaques with ulceration or intraplaque dye penetration by CTA were more voluminous (313±356 mm3 versus 118±93 mm3 P<0.0001), more often positively remodeled (94.5% versus 44.3%, P<0.0001), contained more low-attenuation plaque (99±161 mm3 versus 19±18 mm3, P<0.0001), and were more often complex by ICA (57.8% versus 8.1%, P<0.0001). CTA features of disruption demonstrated modest to good sensitivity (53% to 81%) and good specificity (82% to 95%) for complex plaque by invasive coronary angiography. Conclusions—In this highly selected group of patients with unstable angina, CTA can delineate features of plaque disruption, including ulceration and intraplaque dye penetration, which are specific markers of invasively identified complex plaque. Further studies are needed to confirm the generalizability of the results and to explore the clinical and prognostic implications of these findings.Background— This study was designed as a “proof-of-concept” to establish whether coronary computed tomographic angiography (CTA) has the capability to identify morphological features of plaque disruption. Methods and Results— In patients with unstable angina undergoing CTA and invasive coronary angiography within 30 days, quantitative CTA analysis was performed on all plaques for percent stenosis, volume, remodeling index, and volume of low-attenuation plaque ( 25% stenosis were evaluated for CTA features of disruption, including ulceration and intraplaque dye penetration. Using invasive coronary angiography complex plaque as the reference standard for disruption, the sensitivity and specificity of ulceration and intraplaque dye penetration by CTA were determined. In 60 patients, 294 plaques were identified by CTA, of which 109 (37%) had features of disruption, including ulceration in 53 (18%) lesions and intraplaque dye penetration in 80 (27%). Compared with nondisrupted lesions, plaques with ulceration or intraplaque dye penetration by CTA were more voluminous (313±356 mm3 versus 118±93 mm3 P <0.0001), more often positively remodeled (94.5% versus 44.3%, P <0.0001), contained more low-attenuation plaque (99±161 mm3 versus 19±18 mm3, P <0.0001), and were more often complex by ICA (57.8% versus 8.1%, P <0.0001). CTA features of disruption demonstrated modest to good sensitivity (53% to 81%) and good specificity (82% to 95%) for complex plaque by invasive coronary angiography. Conclusions— In this highly selected group of patients with unstable angina, CTA can delineate features of plaque disruption, including ulceration and intraplaque dye penetration, which are specific markers of invasively identified complex plaque. Further studies are needed to confirm the generalizability of the results and to explore the clinical and prognostic implications of these findings.

Detection by near-infrared spectroscopy of large lipid cores at culprit sites in patients with non-st-segment elevation myocardial infarction and unstable angina

This study was performed to assess the lipid burden of culprit lesions in non‐ST‐segment elevation myocardial infarction (non‐STEMI) and unstable angina (UA).

Analysis of Target Lesion Length Before Coronary Artery Stenting Using Angiography and Near-Infrared Spectroscopy Versus Angiography Alone

Lipid core plaque (LCP) can extend beyond the angiographic margins of a target lesion, potentially resulting in incomplete lesion coverage. We sought to compare the target lesion length using near-infrared spectroscopy (NIRS) combined with conventional coronary angiography versus angiography alone. NIRS was performed in 69 patients (75 lesions) undergoing native vessel percutaneous coronary intervention (LipiScan Coronary Imaging System). Chemograms were analyzed for the presence and location of LCP, either within or extending beyond, the angiographic margins of the target lesion. The target lesion length was measured by quantitative coronary angiography (QCA) and compared to the lesion length measured using QCA and NIRS. LCP was present in 50 target lesions (67%). In 42 lesions (84%), LCP was present only within the target lesion. In 8 lesions (16%) LCP extended beyond the angiographic margins of the lesion. Of these 8 lesions, 4 (8%) had LCP ≤5 mm from the margins, and 4 lesions (8%) had LCP >5 mm from the angiographic margins. The mean distance that the LCP extended beyond the angiographic lesion margin was 7 ± 4 mm (range 2 to 14). For these 8 lesions, the target lesion length with NIRS plus QCA was 28 ± 10 mm versus 21 ± 8 mm with QCA alone. In conclusion, patients undergoing coronary artery stenting could have LCP extending beyond the intended treatment margins as defined using QCA alone. This could have implications for stent length selection and optimal lesion coverage.

Large lipid-rich coronary plaques detected by near-infrared spectroscopy at non-stented sites in the target artery identify patients likely to experience future major adverse cardiovascular events

AIMS A recent study demonstrated that intracoronary near-infrared spectroscopy (NIRS) findings in non-target vessels are associated with major adverse cardiovascular and cerebrovascular events (MACCE). It is unknown whether NIRS findings at non-stented sites in target vessels are similarly associated with future MACCE. This study evaluated the association between large lipid-rich plaques (LRP) detected by NIRS at non-stented sites in a target artery and subsequent MACCE. METHODS AND RESULTS This study evaluated 121 consecutive registry patients undergoing NIRS imaging in a target artery. After excluding stented segments, target arteries were evaluated for a large LRP, defined as a maximum lipid core burden index in 4 mm (maxLCBI4 mm) ≥400. Excluding events in stented segments, Cox regression analysis was performed to evaluate for an association between a maxLCBI4 mm ≥400 and future MACCE, defined as all-cause mortality, non-fatal acute coronary syndrome, and cerebrovascular events. NIRS detected a maxLCBI4 mm ≥400 in a non-stented segment of the target artery in 17.4% of patients. The only baseline clinical variable marginally associated with MACCE was ejection fraction (HR 0.96, 95% CI 0.93-1.00, P = 0.054). A maxLCBI4 mm ≥400 in a non-stented segment at baseline was significantly associated with MACCE during follow-up (HR 10.2, 95% CI 3.4-30.6, P < 0.001). CONCLUSION Detection of large LRP by NIRS at non-stented sites in a target artery was associated with an increased risk of future MACCE. These findings support ongoing prospective studies to further evaluate the ability of NIRS to identify vulnerable patients.

Validity of Estimated Glomerular Filtration Rates for Assessment of Baseline and Serial Renal Function in Patients With Atherosclerotic Renal Artery Stenosis Implications for Clinical Trials of Renal Revascularization

Background— Despite routine use of estimated glomerular filtration rates (GFRs) as major renal end points in clinical trials of renal revascularization, serial GFR estimates have never been validated in patients with renal artery stenosis (RAS). The purpose of this study was to evaluate the validity of GFR estimates in patients with atherosclerotic RAS. Methods and Results— Serum creatinine (SCr) and 125I-iothalamate GFR (I-GFR) were measured in patients with RAS. GFR estimates were calculated from Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), and Cockroft-Gault (CG) formulas. Using I-GFR as the reference standard, the sensitivity, specificity, and receiver operating characteristic area under the curve (AUC) were determined for MDRD, CKD-EPI, CG, and reciprocal SCr for identifying I-GFR <60 mL/min per 1.73 m2 and a 20% change in I-GFR over time. Between 1998 and 2007, 541 I-GFR measurements were performed in 254 consecutive patients with RAS. MDRD, CKD-EPI, and CG GFR estimates demonstrated good sensitivity (86% to 95%), modest specificity (67% to 71%), and good reliability (AUC, 0.86 to 0.94) for identifying I-GFR <60 mL/min per 1.73 m2. GFR estimates had good specificity (87% to 95%), poor sensitivity (0% to 45%), and poor reliability (AUC, 0.61 to 0.65) for detecting 20% changes in I-GFR over follow-up. Conclusions— In patients with RAS, GFR estimates demonstrate good sensitivity and modest specificity for identifying I-GFR <60 mL/min per 1.73 m2 but poor sensitivity and reliability for detecting 20% changes in I-GFR. GFR estimates should not be used in clinical trials as major end points to assess serial GFR after renal revascularization.

Validity of Estimated Glomerular Filtration Rates for Assessment of Baseline and Serial Renal Function in Patients With Atherosclerotic Renal Artery Stenosis

Background— Despite routine use of estimated glomerular filtration rates (GFRs) as major renal end points in clinical trials of renal revascularization, serial GFR estimates have never been validated in patients with renal artery stenosis (RAS). The purpose of this study was to evaluate the validity of GFR estimates in patients with atherosclerotic RAS. Methods and Results— Serum creatinine (SCr) and 125I-iothalamate GFR (I-GFR) were measured in patients with RAS. GFR estimates were calculated from Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), and Cockroft-Gault (CG) formulas. Using I-GFR as the reference standard, the sensitivity, specificity, and receiver operating characteristic area under the curve (AUC) were determined for MDRD, CKD-EPI, CG, and reciprocal SCr for identifying I-GFR <60 mL/min per 1.73 m2 and a 20% change in I-GFR over time. Between 1998 and 2007, 541 I-GFR measurements were performed in 254 consecutive patients with RAS. MDRD, CKD-EPI, and CG GFR estimates demonstrated good sensitivity (86% to 95%), modest specificity (67% to 71%), and good reliability (AUC, 0.86 to 0.94) for identifying I-GFR <60 mL/min per 1.73 m2. GFR estimates had good specificity (87% to 95%), poor sensitivity (0% to 45%), and poor reliability (AUC, 0.61 to 0.65) for detecting 20% changes in I-GFR over follow-up. Conclusions— In patients with RAS, GFR estimates demonstrate good sensitivity and modest specificity for identifying I-GFR <60 mL/min per 1.73 m2 but poor sensitivity and reliability for detecting 20% changes in I-GFR. GFR estimates should not be used in clinical trials as major end points to assess serial GFR after renal revascularization.

Multimodality direct coronary imaging with combined near-infrared spectroscopy and intravascular ultrasound: Initial US experience

Recent studies emphasize the importance of direct intracoronary imaging techniques that provide insights regarding not only lesion architecture but also plaque composition, particularly the presence or absence of lipid‐core plaque (LCP). Intracoronary near‐infrared spectroscopy (NIRS) is the only validated FDA approved device for in vivo detection of LCP. A recently introduced catheter provides simultaneous NIRS spectral data coregistered with standard intravascular ultrasound (IVUS) images in a single intracoronary pullback. The present series of cases illustrates the unique data obtained by this combined NIRS‐IVUS device and highlights its potential clinical applications.