Non-diagnostic coronary artery calcification and stenosis: a correlation of coronary computed tomography angiography and invasive coronary angiography.

Background Heavy coronary artery calcification (CAC) impairs diagnostic accuracy of coronary computed tomography angiography (cCTA) and is considered to be a major limitation. Purpose To investigate the effect of non-evaluable CAC seen on cCTA on clinical decision-making by determining the degree of subsequent invasive testing and to assess the relationship between non-evaluable segments containing CAC and significant stenosis as seen in invasive coronary angiography (ICA). Material and Methods The study comprised of 356 patients who underwent cCTA and subsequent ICA within 2 months between 2005 and 2009. Clinical reports were reviewed to identify the indications for referral to ICA. In a subset of 68 patients where non-diagnostic CAC on cCTA and significant stenosis on ICA were present in the same segment, we correlated and analyzed the underlying stenosis severity of the lesion on ICA to the cCTA. Lesions with CAC were analyzed in a standardized fashion by application of reading rules. Results Non-diagnostic CAC on cCTA prompted ICA in 5.6% of patients. CAC occurred at the site of maximum stenosis in segments with stenosis <50% (95.9% [47/49]), 50-69% (82.4% [28/34]), 70-99% (64.5% [31/48]), and 100% (33.3% [1/3]). At the point of maximum calcium deposit, non-obstructive disease was present in 61.2%. Application of reading rules resulted in a 44% reduction in non-diagnostic cCTA reads. Conclusion Severe CAC may prompt further investigation with ICA. There is less CAC with increasing lesion severity at the point of maximum stenosis. Additional application of reading rules improved non-diagnostic cCTA reads.

Coronary atheroma composition and its association with segmental endothelial dysfunction in non-ST segment elevation myocardial infarction: novel insights with radiofrequency (iMAP) intravascular ultrasonography.

Little is known of the relationship between coronary atheroma composition and corresponding endothelial dysfunction. We tested the hypothesis that segmental epicardial vasoreactivity relates to atheroma composition in patients with non-ST segment elevation myocardial infarction (NSTEMI) in vivo. In 23 NSTEMI patients referred for coronary angiography, a non-culprit vessel underwent intracoronary salbutamol (0.30 µg/min) provocation during automated IVUS pullback. A 40 MHz rotational IVUS catheter delivered radiofrequency signals at constant 67 µm intervals via a custom-built IVUS console (iMAP, iLAB, Boston Scientific). Macrovascular response [change in segmental lumen volume (SLV) at baseline and following salbutamol], percent atheroma volume (PAV) and tissue composition was evaluated in 187 contiguous non-overlapping 5 mm coronary segments. Compared with segments that dilated, constrictive segments showed similar SLV, but greater vessel volumes and PAV at baseline. The extent of necrotic and lipidic plaque was significantly greater in constrictive segments, whereas fibrotic plaque content was significantly greater in segments that dilated. Calcific plaque content did not relate to endothelium-dependent vasoreactivity. The change in SLV correlated inversely with the amount of lipidic and necrotic plaque (both r = -0.23, p = 0.002), and directly with fibrotic plaque content (r = 0.23, p = 0.002). In a multivariable model, the extent of both lipidic and necrotic plaque independently associated with segmental vasoconstriction (ß = 1.2, p = 0.023; ß = 0.66, p = 0.027). Following NSTEMI, both lipidic and necrotic plaque content each associate with segmental endothelial dysfunction. The link between plaque composition and vessel reactivity provides a mechanistic basis of the pathogenesis associated with vulnerable plaque in humans in vivo.

Coronary artery wall shear stress is associated with endothelial dysfunction and expansive arterial remodelling in patients with coronary artery disease.

AIMS: To investigate in vivo relationships between segmental wall shear stress (WSS), endothelium-dependent vasoreactivity and arterial remodelling. METHODS AND RESULTS: Twenty-four patients with minor angiographic coronary arterial disease (≤30% stenosis severity) underwent intracoronary (IC) salbutamol provocation during intravascular ultrasound (IVUS)-upon-Doppler guidewire imaging. Macrovascular response (change in segmental lumen volume [SLV] at baseline and following IC salbutamol), plaque burden (percent atheroma volume [PAV]), remodelling indices (RI), eccentricity indices (EI) and WSS were evaluated in 179 consecutive 5 mm coronary segments. Baseline WSS was directly related to endothelium-dependent epicardial coronary vasomotion (% change SLV, coefficient 17.2, p=0.004), and inversely related to RI (coefficient -0.23, p=0.02) and EI (coefficient -10.0, p=0.001). Baseline WSS was lower in segments displaying endothelial dysfunction (defined as any change in SLV ≤0) compared with preserved function (0.66±0.33 vs. 0.71±0.22 N/m2, p=0.046). Independent of plaque burden, segments with the lowest tertile of WSS displayed less vasodilatation, or vasoconstriction, than segments with the highest tertile of WSS. Higher plaque burden segments harbouring the lowest tertiles of WSS displayed vasoconstriction, expansive arterial remodelling and greater plaque eccentricity. CONCLUSIONS: In patients with stable coronary syndromes and minor angiographic coronary disease, coronary segments with lower in vivo WSS values display functional and morphological features of plaque vulnerability.

Left main coronary arterial endothelial function and heterogenous segmental epicardial vasomotor reactivity in vivo: novel insights with intravascular ultrasonography.

AIMS: While the relationship between epicardial coronary vasomotor reactivity and cardiovascular events is well established, this observation has yet to be evaluated within the left main coronary artery (LMCA) in humans in vivo. Our aims were to test the endothelium-dependent vasomotor properties of the LMCA, and to compare these responses to downstream epicardial segments. METHODS AND RESULTS: Thirty patients referred for coronary angiography underwent intracoronary (IC) salbutamol provocation during intravascular ultrasound imaging within a non-critically diseased, left-sided conduit vessel. Macrovascular vasomotor response [change in average lumen area (LA) at baseline and following 5 min of 0.30 µg/min IC salbutamol] and percent atheroma volume (PAV) were evaluated in 30 LMCA, 42 proximal, 109 mid, and 132 distal epicardial coronary segments. In comparison with all other segments, the LMCA had the greatest lumen and vessel areas (P < 0.001), yet the proximal epicardial segments contained the greatest PAV (P < 0.02). The mid and distal epicardial segments displayed significant endothelium-dependent vasodilatation from baseline (P = 0.017 and <0.001, respectively); however, the proximal epicardial and LMCA segments did not (P = 0.45 and 0.16, respectively). Significant segmental vasomotor heterogeneity was noted in all 30 patients, with opposing vasomotor responses between adjacent LMCA and epicardial segments. Across all segments, baseline LA inversely correlated with the % change in LA (r = -0.16, P = 0.0005). CONCLUSION: Endothelium-dependent vasomotor reactivity is heterogenous within the conduit coronary system. Vascular dynamic responses were less prominent in the larger calibre LMCA and proximal epicardial segments. This may, in part, relate to higher shear stress in smaller, distal segments and yet also may explain the propensity for culprit plaques to cluster proximally.

Coronary endothelium-dependent vasoreactivity and atheroma volume in subjects with stable, minimal angiographic disease versus non-ST-segment-elevation myocardial infarction: an intravascular ultrasound study.

BACKGROUND: Epicardial plaque burden and endothelial function are recognized predictors of coronary events. We aimed to investigate mechanistic relationships between atheroma volume and endothelial function in patients with non-ST-segment-elevation myocardial infarction (NSTEMI) using intravascular ultrasound. METHODS AND RESULTS: In coronary vessels of patients with near-normal or minimal angiographic disease (n=23) and NSTEMI (n=24), intravascular ultrasound-derived measures (percent atheroma volume), arterial remodeling index, and segmental lumen volumes were performed in contiguous 5-mm epicardial segments. Repeat intravascular ultrasound imaging was performed after consecutive 5-minute intracoronary infusions (vehicle solution, 0.30 µg/min and 0.60 µg/min intracoronary salbutamol) to measure changes in segmental lumen volume (endothelium-dependent function). Male sex, diabetes mellitus, smoking, higher triglycerides, and lower high-density lipoprotein cholesterol were more prevalent in the NSTEMI group. Patients with NSTEMI demonstrated greater segmental percent atheroma volume (40.4 ± 12 versus 27.5 ± 14%, P<0.001), remodeling index (1.2 [1.0-1.5] versus 1.0 [0.9-1.0], P<0.001), and displayed less endothelium-dependent vasomotion (% change segmental lumen volume: 2.1 ± 0.89 versus 5.1 ± 0.89%, P=0.02) compared to patients with minimal angiographic disease. No significant difference in endothelial function between both groups was observed when controlling for plaque burden. Multivariate analysis for change in segmental lumen volume identified percent atheroma volume (ß=-0.18, P=0.0004), high-sensitivity C-reactive protein >2 mg/L (ß=-3.1, P=0.03), diabetes mellitus (ß=-6.9, P<0.0001), low-density lipoprotein cholesterol levels (ß=-0.04, P=0.01), and smoking (ß=-3.2, P=0.01) as independent associates. CONCLUSIONS: Although coronary endothelial vasoreactivity is blunted in the setting of NSTEMI, this is a reflection of the greater volume of atherosclerosis and cardiovascular risk factors. Thus, the relationship between coronary endothelium-dependent vasomotor reactivity and atheroma volume remains constant irrespective of the nature of the clinical presentation.

Relationship of aortic annular eccentricity and paravalvular regurgitation post transcatheter aortic valve implantation with CoreValve.

BACKGROUND: Significant paravalvular aortic regurgitation (PAR) after transcatheter aortic valve implantation (TAVI) is associated with negative clinical consequences. We hypothesize that increased eccentricity of the aortic annulus is associated with greater PAR. METHODS: Patients with severe aortic stenosis underwent multidetector computed tomography (MDCT) before successful TAVI with the Medtronic CoreValve bioprosthesis. The smallest (D(min)) and largest (D(max)) orthogonal diameters in the basal ring of the aortic annulus were determined. We defined circularity of aortic annulus using the eccentricity index (1 - D(min)/D(max)). The primary endpoint was early occurrence of significant PAR, defined as > grade II PAR by postprocedural aortography. RESULTS: Eighty-four patients, mean age 83 ± 4 years with a mean aortic valve area of 0.7 ± 0.2 cm² were included. Twenty patients had postprocedural PAR > grade II. Using a receiver operating characteristic (ROC) analysis, eccentricity index correlated with significant PAR (AUC = 0.834; P=.034). A retrospectively determined eccentricity index cut-off of >0.25 was related to significant PAR with a sensitivity of 80%, specificity of 86%, and negative predictive value of 95% (P<.001). On univariate logistic regression, eccentricity index of >0.25 (P<.001) and device implantation depth (P=.015) correlated with significant PAR, while other parameters such as annular calcification and cover index did not. On multivariate analysis including only parameters with P<.1 on univariate analysis, eccentricity index >0.25 was the sole independent predictor of significant PAR. CONCLUSION: Eccentricity index is related to significant PAR after TAVI with Medtronic CoreValve. Further larger studies are required to determine the utility of this novel index in screening suitable patients for this procedure.

Intracoronary ECG during primary percutaneous coronary intervention for ST-segment elevation myocardial infarction predicts microvascular obstruction and infarct size.

INTRODUCTION: Microvascular obstruction (MVO) following ST-segment elevation myocardial infarction (STEMI) is associated with larger infarct size and an increased mortality. Although angiographic predictors of MVO in primary percutaneous coronary intervention (primary-PCI) setting have been identified, an earlier and objective "in-lab" predictor may be beneficial, in order to potentially influence therapies administered during primary-PCI. We hypothesised that intracoronary-electrocardiogram (IC-ECG) is a simple, objective and accurate predictor of MVO evaluated by cardiac magnetic resonance (CMR) and is comparable to myocardial blush grade (MBG) and TIMI myocardial perfusion grade (TMPG). METHOD: Intracoronary ECG was performed during primary-PCI. Intracoronary ST-segment measurement was performed before and immediately after opening of infarct-related-artery. Intracoronary ST-segment resolution (IC-STR) was defined as ≥ 1 mm improvement compared to baseline. Contrast enhanced CMR was performed at 4 and 90 days post primary-PCI. Primary endpoint was MVO on late gadolinium hyperenhancement assessed by CMR at day 4. RESULTS: Sixty-four consecutive patients (age 59 ± 11 years; 55 males) were recruited. Intracoronary ST-segment resolution correlated with MVO (p=0.005). Furthermore, IC-STR correlated with infarct-mass, non-viable-mass, peak creatinine kinase and end-systolic-volume at day 4. Intracoronary ST-segment resolution also correlated with favourable left ventricular end-diastolic-volume at day 90 (p=0.022). On multivariate analysis, IC-STR was an independent predictor of MVO. CONCLUSION: Intracoronary ST-segment resolution is a strong in-lab predictor of MVO assessed 4 days after STEMI on CMR. Furthermore, IC-STR correlates with infarct size and left ventricular remodelling at 3 months. Further studies are required to understand potential clinical utility of this tool.

Intracoronary ECG ST-segment recovery during primary percutaneous intervention for ST-segment myocardial infarction: insights from a cardiac MRI study.

BACKGROUND: ST-segment-resolution (STR) on surface electrocardiogram (ECG) is a good surrogate for myocardial reperfusion in patients with acute ST-segment-elevation-myocardial-infarction (STEMI). We sort to determine the optimal criteria of measuring STR on intracoronary-ECG (IC-ECG) for prediction of myocardial injury evaluated by cardiac MRI (CMR). METHODS: Measurements of IC-ECG ST-segments were performed at baseline, immediately after (early) and 15 min (late) after achieving TIMI-3 flow during primary-PCI. The degree of ST-segment-shift from baseline noted upon the IC-ECG was divided into four groups: (group 1) ST-segment-resolution >1 mm, (group 2) <30% resolution, (group 3) >50% resolution, (group 4) >70% resolution at both early and late time points. Patients had CMR at days 3 and 90 postprimary-PCI. RESULTS: Fifty two patients (aged 60 ± 11 years; 43 males) were evaluated. Early intracoronary-ECG ST-segment resolution (early IC-STR >1 mm) correlated with smaller scar mass (P = 0.003), nonviable myocardial mass (P < 0.001), and microvascular obstruction (MVO) (P = 0.004) on CMR at day 3. Ejection fraction (EF) was also better at day 3 (P = 0.026) and 90 (P = 0.039). Patients with poor early IC-STR (IC-STR <30%) conversely is associated with larger scar mass (P = 0.017), nonviable myocardial mass (P = 0.01), and MVO (P = 0.021) at day 3. This was also associated with worse EF at day 90 (P = 0.044). Neither group 3 or 4, or the late measurements of late IC-STR correlated with CMR markers of myocardial injury. CONCLUSION: The degree of early IC-STR (defined by IC-STR > 1 mm or <30%) successfully predicts myocardial damage following primary-PCI for an acute STEMI. Further studies are required to investigate its potential utility.

Appropriate indications for computed tomography coronary angiography.

Computed tomography coronary angiography (CTCA) has been shown in multicentre trials to be reliable in ruling out significant coronary artery disease (CAD). It is used most appropriately in symptomatic patients with low to intermediate pretest probability of CAD. It should not be used in asymptomatic subjects, patients with known significant CAD or patients with a high pretest probability of CAD. The radiation dose of CTCA was previously two to three times that of invasive coronary angiography but with modern protocols, it is similar or lower. Patients generally need to be in sinus rhythm, tolerate Β-blockers and nitrates, have a heart rate < 65 beats per minute, be able to hold their breath for 10 seconds, and have normal renal function.

Aortic annulus dimension assessment by computed tomography for transcatheter aortic valve implantation: differences between systole and diastole.

Accurate assessment of aortic annular dimensions is essential for successful transcatheter aortic valve implantation (TAVI). Annular dimensions are conventionally measured in mid-systole by multidetector computed tomography (MDCT), echocardiography and angiography. Significant differences in systolic and diastolic aortic annular dimensions have been demonstrated in cohorts without aortic stenosis (AS), but it is unknown whether similar dynamic variation in annular dimensions exists in patients with severe calcific AS in whom aortic compliance is likely to be substantially reduced. We investigated the variation in aortic annular dimensions between systole and diastole in patients with severe calcific AS. Patients with severe calcific AS referred for TAVI were evaluated by 128-slice MDCT. Aortic annular diameter was measured during diastole and systole in the modified coronal, modified sagittal, and basal ring planes (maximal, minimal and mean diameters). Differences between systole and diastole were analysed by paired t test. Fifty-nine patients were included in the analysis. Three of the five aortic dimensions measured increased significantly during systole. The largest change was a 0.75 mm (3.4%) mean increase in the minimal diameter of the basal ring during systole (p = 0.004). This corresponds closely to the modified sagittal view, which also increased by mean 0.42 mm (1.9%) during systole (p = 0.008). There was no significant change in the maximal diameter of the basal ring or the modified coronal view during systole (p > 0.05). There is a small magnitude but statistically significant difference in aortic annulus dimensions of patients with severe AS referred for TAVI when measured in diastole and systole. This small difference is unlikely to alter clinical decisions regarding prosthesis size or suitability for TAVI.

Coronary ß2-adrenoreceptors mediate endothelium-dependent vasoreactivity in humans: novel insights from an in vivo intravascular ultrasound study.

AIMS: The interaction between coronary ß(2)-adrenoreceptors and segmental plaque burden is complex and poorly understood in humans. We aimed to validate intracoronary (IC) salbutamol as a novel endothelium-dependent vasodilator utilizing intravascular ultrasound (IVUS), and thus assess relationships between coronary ß(2)-adrenoreceptors, regional plaque burden and segmental endothelial function. METHODS AND RESULTS: In 29 patients with near-normal coronary angiograms, IVUS-upon-Doppler Flowire imaging protocols were performed. Protocol 1: incremental IC salbutamol (0.15, 0.30, 0.60 µg/min) infusions (15 patients, 103 segments); protocol 2: salbutamol (0.30 µg/min) infusion before and after IC administration of N(G)-monomethyl-L-arginine (L-NMMA) (10 patients, 82 segments). Vehicle infusions (IC dextrose) were performed in 4 patients (21 segments). Macrovascular response [% change segmental lumen volume (ΔSLV)] and plaque burden [per cent atheroma volume (PAV)] were studied in 5-mm coronary segments. Microvascular response [per cent change in coronary blood flow (ΔCBF)] was calculated following each infusion. Intracoronary salbutamol demonstrated significant dose-response ΔSLV and ΔCBF from baseline, respectively (0.15 µg/min: 3.5 ± 1.3%, 28 ± 14%, P = 0.04, P = NS; 0.30 µg/min: 5.5 ± 1.4%, 54 ± 17%, P = 0.001, P < 0.0001; 0.60 µg/min: 4.8 ± 1.6%, 66 ± 15%, P = 0.02, P < 0.0001), with ΔSLV responses further exemplified in low vs. high plaque burden groups. Salbutamol vasomotor responses were suppressed by l-NMMA, supporting nitric oxide-dependent mechanisms. Vehicle infusions resulted in no significant ΔSLV or ΔCBF. Multivariate analysis including conventional cardiovascular risk factors, PAV, segmental remodelling and plaque eccentricity indices identified PAV as the only significant predictor of a ΔSLV to IC salbutamol (coefficient -0.18, 95% CI -0.32 to -0.044, P = 0.015). Conclusions Intracoronary salbutamol is a novel endothelium-dependent epicardial and microvascular coronary vasodilator. Intravascular ultrasound-derived regional plaque burden is a major determinant of segmental coronary endothelial function.

Diagnostic accuracy of adenosine stress cardiovascular magnetic resonance following acute ST-segment elevation myocardial infarction post primary angioplasty.

BACKGROUND: Adenosine stress cardiovascular magnetic resonance (CMR) has been proven an effective tool in detection of reversible ischemia. Limited evidence is available regarding its accuracy in the setting of acute coronary syndromes, particularly in evaluating the significance of non-culprit vessel ischaemia. Adenosine stress CMR and recent advances in semi-quantitative image analysis may prove effective in this area. We sought to determine the diagnostic accuracy of semi-quantitative versus visual assessment of adenosine stress CMR in detecting ischemia in non-culprit territory vessels early after primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI). METHODS: Patients were prospectively enrolled in a CMR imaging protocol with rest and adenosine stress perfusion, viability and cardiac functional assessment 3 days after successful primary-PCI for STEMI. Three short axis slices each divided into 6 segments on first pass adenosine perfusion were visually and semi-quantitatively analysed. Diagnostic accuracy of both methods was compared with non-culprit territory vessels utilising quantitative coronary angiography (QCA) with significant stenosis defined as ≥ 70%. RESULTS: Fifty patients (age 59 ± 12 years) admitted with STEMI were evaluated. All subjects tolerated the adenosine stress CMR imaging protocol with no significant complications. The cohort consisted of 41% anterior and 59% non anterior infarctions. There were a total of 100 non-culprit territory vessels, identified on QCA. The diagnostic accuracy of semi-quantitative analysis was 96% with sensitivity of 99%, specificity of 67%, positive predictive value (PPV) of 97% and negative predictive value (NPV) of 86%. Visual analysis had a diagnostic accuracy of 93% with sensitivity of 96%, specificity of 50%, PPV of 97% and NPV of 43%. CONCLUSION: Adenosine stress CMR allows accurate detection of non-culprit territory stenosis in patients successfully treated with primary-PCI post STEMI. Semi-quantitative analysis may be required for improved accuracy. Larger studies are however required to demonstrate that early detection of non-culprit vessel ischemia in the post STEMI setting provides a meaningful test to guide clinical decision making and ultimately improved patient outcomes.

In vivo non-invasive serial monitoring of FDG-PET progression and regression in a rabbit model of atherosclerosis.

We investigated the ability of fluorodeoxyglucose positron emission tomography (FDG PET) imaging to serially monitor macrophage content in a rabbit model of atherosclerosis. Atherosclerosis was induced in rabbits (n = 8) by a combination of atherogenic diet and balloon denudation of the aorta. At the end of nine months, the rabbits were randomized to a further six months of the same atherogenic diet (progression group) or normal diet (regression group). In vivo uptake of FDG by the thoracic aorta was measured using aortic uptake-to-blood radioactivity ratios at the start and end of the randomized period. A significant increase in FDG uptake of the progression group after continued cholesterol feeding (aortic uptake-to-blood radioactivity: 0.57 +/- 0.02 to 0.68 +/- 0.02, P = 0.001), and a corresponding fall in FDG uptake of the regression group after returning to a normal chow diet (aortic uptake-to-blood radioactivity ratios: 0.67 +/- 0.02 to 0.53 +/- 0.02, P < 0.0001). FDG PET can quantify in vivo macrophage content and serially monitor changes in FDG activity in this rabbit model.