Fractional flow reserve derived from coronary computed tomography angiography reclassification rate using value distal to lesion compared to lowest value.

INTRODUCTION: A standardised approach to the interpretation of FFRCT data is currently lacking. We evaluated the rate of reclassification of FFRCT positivity using the FFRCT value distal to an anatomical stenoses compared to the lowest FFRCT value. METHOD: Patients who underwent coronary CTA and FFRCT analysis were eligible. FFRCT value of ≤ 0.80 was considered positive. Positive FFRCT distal to stenosis was defined as those with a stenoses of ≥ 25% with an associated FFRCT value of ≤ 0.80 within 2cm distal to the lesion. Outcome data on subsequent invasive coronary angiography (ICA) and coronary revascularisation were collected with a minimum follow-up of 60 days to account for delay between referral for invasive testing and/or revascularisation and receiving the procedure. RESULT: 192 patients (mean age 60.7 ± 10.6 years, 67.5% men) were included. FFRCT was positive for lowest FFRCT value in 55.7% of patients. Positive FFRCT value distal to stenosis was found in 31.3%. The overall reclassification rate of those positive for lowest FFRCT value to negative for FFRCT value distal to stenosis was 43.9% (p < 0.01). The reclassification rates were most pronounced for those with intermediate stenoses - 67% for those with < 50% stenoses, p < 0.01; 49% for 50-69% stenoses, p < 0.01. Amongst those who underwent ICA, the rate of revascularization was significant higher for those with positive FFRCT distal to stenosis compared to those positive for lowest FFRCT value (revascularization/ICA = 0.53 vs 0.44, p < 0.01). CONCLUSION: Using FFRCT values distal to a anatomical stenoses, 44% of patients positive for lowest FFRCT value were reclassified as negative for FFRCT value distal to stenosis. Those who underwent ICA, the rate of revascularisation was higher amongst those with positive FFRCT distal to stenosis compared to those positive for lowest FFRCT value.

Prospective Assessment of the Diagnostic Accuracy of Instantaneous Wave-Free Ratio to Assess Coronary Stenosis Relevance: Results of ADVISE II International, Multicenter Study (ADenosine Vasodilator Independent Stenosis Evaluation II).

OBJECTIVES: The purpose of this study was to assess the diagnostic accuracy of the instantaneous wave-free ratio (iFR) to characterize, outside of a pre-specified range of values, stenosis severity, as defined by fractional flow reserve (FFR) ≤0.80, in a prospective, independent, controlled, core laboratory-based environment. BACKGROUND: Studies with methodological heterogeneity have reported some discrepancies in the classification agreement between iFR and FFR. The ADVISE II (ADenosine Vasodilator Independent Stenosis Evaluation II) study was designed to overcome limitations of previous iFR versus FFR comparisons. METHODS: A total of 919 intermediate coronary stenoses were investigated during baseline and hyperemia. From these, 690 pressure recordings (n = 598 patients) met core laboratory physiology criteria and are included in this report. RESULTS: The pre-specified iFR cut-off of 0.89 was optimal for the study and correctly classified 82.5% of the stenoses, with a sensitivity of 73.0% and specificity of 87.8% (C statistic: 0.90 [95% confidence interval (CI): 0.88 to 0.92, p < 0.001]). The proportion of stenoses properly classified by iFR outside of the pre-specified treatment (≤0.85) and deferral (≥0.94) values was 91.6% (95% CI: 88.8% to 93.9%). When combined with FFR use within these cut-offs, the percent of stenoses properly classified by such a pre-specified hybrid iFR-FFR approach was 94.2% (95% CI: 92.2% to 95.8%). The hybrid iFR-FFR approach obviated vasodilators from 65.1% (95% CI: 61.1% to 68.9%) of patients and 69.1% (95% CI: 65.5% to 72.6%) of stenoses. CONCLUSIONS: The ADVISE II study supports, on the basis rigorous methodology, the diagnostic value of iFR in establishing the functional significance of coronary stenoses, and highlights its complementariness with FFR when used in a hybrid iFR-FFR approach. (ADenosine Vasodilator Independent Stenosis Evaluation II-ADVISE II; NCT01740895).

Additional value of adenosine-stress dynamic CT myocardial perfusion imaging in the reclassification of severity of coronary artery stenosis at coronary CT angiography.

AIM: To assess the additional value of adenosine-stress dynamic computed tomography (CT) perfusion (ASDCTP) imaging compared with coronary CT angiography (CCTA) alone to detect significant coronary artery stenosis for each threshold of 50% and 70% diameter stenosis. MATERIALS AND METHODS: The study included 34 patients (65 ± 11 years, 79% men) with suspected coronary artery diseases who underwent ASDCTP imaging using a 128-section dual-source CT (DSCT) and invasive coronary angiography (ICA). Two investigators classified coronary artery stenosis on CCTA as severe or not. If appropriate image quality could not be acquired due to artefacts, the segment was classified as a lesion with significant stenosis. After the interpretation of ASDCTP imaging, the degree of stenosis was reclassified. All parameters of diagnostic accuracy were calculated before and after ASDCTP analysis for detection of significant coronary artery stenosis with ICA as the reference standard. RESULTS: The diagnostic accuracy parameters per vessel for the detection of ≥50% stenosis before and after ASDCTP analysis changed as follows: sensitivity, from 80% to 83%; specificity, from 83% to 98%; positive predictive value (PPV), from 87% to 98%; and negative predictive value (NPV), from 75% to 80%. The addition of ASDCTP resulted in reclassification from one class of stenosis severity to another in a significant number of vessels with threshold of 50% stenosis [net reclassification improvement (NRI), 0.176; p < 0.01]. Conversely, the addition of ASDCTP did not result in significant reclassification of stenosis severity in vessels with threshold of 70% stenosis (NRI, 0.034; p = 0.51). CONCLUSIONS: ASDCTP imaging provides incremental value in the detection of significant coronary artery stenosis using a threshold of 50%.

Definitions and methodology for the grayscale and radiofrequency intravascular ultrasound and coronary angiographic analyses.

OBJECTIVES: In a prospective study of the natural history of coronary atherosclerosis using angiography and grayscale and radiofrequency intravascular ultrasound (IVUS)-virtual histology (VH), larger plaque burden, smaller luminal area, and plaque composition thin-cap fibroatheroma emerged as independent predictors of future adverse cardiovascular events. BACKGROUND: The methodology for IVUS-VH classification for an in vivo natural history study and the prospective image mapping by angiography and grayscale and IVUS-VH have not been established. METHODS: All culprit and nonculprit lesions (defined as ≥ 30% angiographic visual diameter stenoses) were analyzed. Three epicardial vessels as well as all ≥ 1.5-mm-diameter side branches were divided into 29 CASS (Coronary Artery Surgery Study) segments. Each CASS segment was then subdivided into 1.5-mm-long subsegments, and dimensions were analyzed. All grayscale and IVUS-VH slices from the proximal 6 to 8 cm of the 3 coronary arteries were analyzed, with lesions defined as having more than 3 consecutive slices with ≥ 40% plaque burden categorized as: 1) VH thin-cap fibroatheroma; 2) thick-cap fibroatheroma; 3) pathological intimal thickening; 4) fibrotic plaque; or 5) fibrocalcific plaque. The locations of angiographic and grayscale and IVUS-VH lesions were recorded in relation to the corresponding coronary artery ostium and nearby side branches. RESULTS: The 3-year cumulative rate of major adverse cardiovascular events was 20.4%. Events were adjudicated to culprit lesions in 12.9% of patients and to nonculprit lesions in 11.6%. On multivariate analysis, nonculprit lesions associated with recurrent events were characterized by a plaque burden ≥ 70% (hazard ratio: 5.03; 95% confidence interval: 2.51 to 10.11; p < 0.0001), a minimal luminal area ≤ 4.0 mm(2) (hazard ratio: 3.21; 95% confidence interval: 1.61 to 6.42; p = 0.001), and IVUS-VH phenotype of a thin-cap fibroatheroma (hazard ratio: 3.35; 95% confidence interval: 1.77 to 6.36; p < 0.001). CONCLUSIONS: Three-vessel multimodality coronary artery imaging was feasible and allowed the identification of lesion-level predictors for future events in this natural history study.

Periodontal disease in association with systemic levels of interleukin-18 and CXC ligand 16 in patients undergoing cardiac catheterization.

BACKGROUND: Interleukin (IL)-18 is a proinflammatory cytokine that is present in chronically inflamed tissues; IL-18 was positively associated with periodontitis and coronary artery disease (CAD). CXC ligand (CXCL) 16, a recently discovered chemokine, was identified in atherosclerotic lesions; its role in periodontal disease is largely unknown. This research study correlates periodontal parameters with systemic levels of IL-18 and CXCL16. METHODS: Fifty-one patients who presented for clinically indicated coronary angiography received full-mouth periodontal examinations. The periodontal status of patients was defined using frequency distributions of probing depth (PD), clinical attachment loss (AL), and bleeding on probing (BOP). Blood samples were collected during cardiac catheterization, and plasma levels of IL-18 and CXCL16 were analyzed. The severity of CAD was determined by the presence and extent of coronary artery stenosis. Correlations between periodontal parameters, levels of inflammatory mediators, and CAD status were analyzed. RESULTS: The extent of BOP exhibited a significant positive correlation with IL-18 in the Spearman rank correlation analysis (P = 0.039), which indicated a correlation between periodontal inflammation and systemic IL-18 levels. When multiple regression analysis was performed, the extent of clinical AL > or =3 mm (P = 0.045) and > or =5 mm (P = 0.024) exhibited an association with IL-18, whereas CXCL16 was associated with clinical AL > or =5 mm (P = 0.040) and PD > or =7 mm (P = 0.047). CONCLUSION: A significant correlation is identified between periodontitis and systemic levels of IL-18 and CXCL16 in patients undergoing diagnostic coronary angiography.

Atherosclerotic plaque composition among patients with stenotic coronary artery disease on noninvasive CT angiography.

INTRODUCTION: Multidetector computed tomographic angiography (MDCTA) has emerged as a promising noninvasive tool to rule out significant coronary artery disease (CAD). In addition, MDCTA also provides additional information about atherosclerotic plaque composition. In this study, we aim to assess whether differences in plaque composition exist across patients with varying degree of stenotic CAD disease. METHODS: Four hundred and sixteen patients with chest pain or shortness of breath thought to be related to CAD (64% males, mean age: 61+/-13 years), with 61 (15%) reporting type 2 diabetes mellitus, who underwent contrast-enhanced MDCTA were studied. Enrolled patients had an intermediate pretest probability of obstructive disease. RESULTS: Overall 51 patients (12%) had normal coronaries without evidence of plaque. In the remaining 365 patients, 45 (12%) and 83 (23%) were found to have stenosis 50-70% and at least 70% in at-least one coronary artery segment, respectively. Those with a higher degree of stenotic CAD showed significantly more coronary segments with exclusively calcified and mixed plaques. With increasing severity of CAD (<50 vs. 50-70% vs. >70% stenosis), the overall proportion of plaque burden was more likely to be mixed (18 vs. 38% vs. 44%) in nature as well less likely to be exclusively noncalcified (39 vs. 20 vs. 16%). Only two of 108 (2%) patients without any underlying calcification had significant CAD (stenosis> or =50%). CONCLUSION: Significant differences in plaque composition according to severity of CAD were observed in our study. Individuals with a higher likelihood of stenotic CAD were more likely to have higher underlying burden of exclusively calcified and mixed plaque. These findings should stimulate further investigations to assess the prognostic value of plaque according to their underlying composition.

Comparison of outcomes of percutaneous coronary intervention on proximal versus non-proximal left anterior descending coronary artery, proximal left circumflex, and proximal right coronary artery: a cross-sectional study.

BACKGROUND: Previous studies have shown that lesions in proximal left anterior descending coronary artery (LAD) may develop more restenosis after balloon angioplasty than lesions in other coronary segments. However, stenting seems to have reduced this gap. In this study, we compared outcomes of percutaneous coronary intervention (PCI) on proximal LAD versus proximal left circumflex (LCX) or right coronary artery (RCA) and proximal versus non-proximal LAD. METHODS: From 1737 patients undergoing PCI between March 2004 and 2005, those with cardiogenic shock, primary PCI, total occlusions, and multivessel or multi-lesion PCI were excluded. Baseline characteristics and in-hospital outcomes were compared in 408 patients with PCI on proximal LAD versus 133 patients with PCI on proximal LCX/RCA (study I) and 244 patients with PCI on non-proximal LAD (study II). From our study populations, 449 patients in study I and 549 patients in study II participated in complete follow-up programs, and long-term PCI outcomes were compared within these groups. The statistical methods included Chi-square or Fisher's exact test, student's t-test, stratification methods, multivariate logistic regression and Cox proportional hazards model. RESULTS: In the proximal LAD vs. proximal LCX/RCA groups, smoking and multivessel disease were less frequent and drug-eluting stents were used more often (p = 0.01, p < 0.001, and p < 0.001, respectively). Patients had longer and smaller-diameter stents (p = 0.009, p < 0.001, respectively). In the proximal vs. non-proximal LAD groups, multivessel disease was less frequent (p = 0.05). Patients had larger reference vessel diameters (p < 0.001) and were more frequently treated with stents, especially direct stenting technique (p < 0.001). Angiographic success rate was higher in the proximal LAD versus proximal LCX/RCA and non-proximal LAD groups (p = 0.004 and p = 0.05, respectively). In long-term follow-up, major adverse cardiac events showed no difference. After statistical adjustment for significant demographic, angiographic or procedural characteristics, long-term PCI outcomes were still similar in the proximal LAD versus proximal LCX/RCA and non-proximal LAD groups. CONCLUSION: Despite the known worse prognosis of proximal LAD lesions, in the era of stenting, our long-term outcomes were similar in patients with PCI on proximal LAD versus proximal LCX/RCA and non-proximal LAD. Furthermore, we had better angiographic success rates in patients with PCI on proximal LAD.

Concomitant presence of subtypes of left coronary artery disease.

OBJECTIVE: To study the risk profile associated with surgical revascularization for mixed left main and left main equivalent diseases. METHODS AND RESULTS: Retrospective analysis of medical records of patients who underwent CABG from January 1997 and December 2002 were studied. 210 patients were included of which 30.5% (64) had left main, 49.5% (104) had left main equivalent and 20% (42) had mixed type of stenotic disease. The mixed type left coronary disease was associated with very high post-operative mortality. The factors associated with mortality were degree of left main artery stenosis, cardiopulmonary bypass pump time, no. of packed cell units transfused during surgery, post-operative low cardiac output, re-exploration of chest and no. of days spent as intubated. Low cardiac output, chest re-exploration and no. of days intubated were independently associated with mortality. CONCLUSIONS: "Mixed left main and left main equivalent disease" makes a large proportion of left sided CAD. It is a unique subtype associated with very high risk, and it should be treated with extra caution. Characterization of its risk profile should be done with larger studies to improve the outcome.

Late results after PTCA for coronary stenosis after the arterial switch procedure for transposition of the great arteries.

BACKGROUND: The arterial switch operation has become the surgical approach of choice for d-transposition of the great arteries, but there is an increased awareness of adverse sequelae in some survivors. Long-term patency and normal function of the translocated coronary arteries must be achieved. It is reported that dependent of the prior coronary status, 3% to 11% of all survivors have proximal coronary stenosis or complete occlusion develop after arterial switch operations. However, treatment of these stenoses is still a matter of debate. Late results after percutaneous transluminal coronary angioplasty (PTCA) for coronary stenosis after the arterial switch operation for d-transposition of the great arteries are reported. METHODS: Seven children after arterial switch operation for d-transposition of the great arteries who had subsequently undergone PTCA for coronary stenosis were angiographically re-evaluated 3 to 15 months after the initial PTCA and again after 3 to 5 years. RESULTS: All children survived the initial PTCA procedure. There were no late deaths. The degree of stenosis before PTCA ranged from 74% to 97%; immediately after PTCA from 5% to 10%; at 3 to 15 months after PTCA from zero to 6%; and at 3 to 5 years after PTCA from zero to 3%. Three to 5 years after PTCA all children showed normal development of the treated coronary artery. CONCLUSIONS: Primary PTCA of stenotic proximal coronary arteries after the arterial switch procedure for d-transposition of the great arteries seems to be an effective treatment with excellent long-term results.

Differential outcome after intracoronary radiation therapy is related to a simple classification based on lesion length and reference diameter.

OBJECTIVE: We sought to develop a prognostic lesion classification based on simple angiographic parameters, lesion length and reference diameter that predicts differential outcome in patients undergoing intracoronary radiation. METHODS AND RESULTS: Three types of lesions were identified: Type A characterized by lesion length less than or equal to 30 mm, reference diameter > 2.5 mm to less than or equal to 4.0 mm (short lesion: normal diameter), Type B by lesion length less than or equal to 30 mm, reference diameter less than or equal to 2.5 mm or > 4 mm (short lesion: extreme diameter), and Type C by lesion length > 30 mm (long lesion). A total of 1,151 lesions (77.7% in-stent restenosis) in 1,098 consecutive patients undergoing brachytherapy were classified into these 3 lesion types. Overall, 79.9%, 10.3% and 9.8% patients met the criteria for Type A, B and C lesions. While the in-hospital major adverse cardiac event (MACE) rate was 1.4%, 3.6% and 3.8% (p = 0.026), the 6-month MACE rate was 16.1%, 22.5% and 32.1% (p < 0.001), the angiographic restenosis rate was 21.3%, 32.4% and 42.4% (p < 0.001), and the late thrombosis rate was 4.1%, 9.0% and 11.3%, (p < 0.001) in Type A, B and C lesions, respectively. Consequently, with increasing lesion severity, 3 risk groups with low, medium and high risk were defined. Multivariate analysis showed that Type B and C lesions were independent predictors of 6-month MACE (OR, 1.5 and 1.9, respectively). CONCLUSION: The proposed novel and easily applicable lesion classification effectively predicts early and medium term outcome, and may be used for appropriate therapeutic decision making in patients undergoing brachytherapy.

Coronary bifurcation stenting. Current techniques, outcome and possible future developments.

Percutaneous treatment of coronary bifurcation lesions remained challenging in the stent era, with restenosis rates greater than 30% and no advantage from the routine use of kissing stents. Drug eluting stents (DES) have dramatically reduced the restenosis rates (RR) in the main vessel, but with conventional T-stenting double digits figures are still reported for the side-branch because of poor ostial coverage. The techniques of kissing stenting able to provide full lesion coverage (Culotte, V-stenting, Crush) have the potential to improve these results but the development of dedicated DES is probably needed to obtain consistently high procedural and long-term success.

[Evaluating multislice computed tomography for imaging coronary atherosclerosis]. / Evaluierung der Mehrzeilendetektorcomputertomographie zur Darstellung der koronaren Atherosklerose.

PURPOSE: The purpose of this study was the evaluation of multidetector-row computed tomography (MDCT) for the assessment of atherosclerotic coronary artery vessel wall changes. METHODS: In an ex vivo study, 17 human hearts were scanned with MDCT and results were compared to histopathology. Morphologic imaging criteria of MDCT for various plaque-types were developed. In a following in vivo study, 94 coronary MDCT angiograms (MDCTA) of patients with suspected coronary artery disease (CAD) were reviewed retrospectively, assessing the diagnostic value of the coronary MDCTA, and determining the number and correlations of the various plaques types as described in the ex vivo study. Additionally, volumetry of calcified and noncalcified plaque components was performed. RESULTS: In the ex vivo study, MDCT showed a high sensitivity for calcified and non-calcified plaques. Comparing the results with histopathology, characteristic image criteria could be determined for lipid-rich, fibrous and calcified plaque components. Reviewing the contrastenhanced in-vivo MDCT coronary angiographies, presence of noncalcified plaques was proven in 38% of the patients. In 5 patients with a calcium score of 0, presence of coronary atherosclerosis was proven in the contrastenhanced scan. CONCLUSIONS: MDCT is able to differentiate various plaque components in an ex vivo setting as well as invivo. Contrastenhanced MDCT of the coronary arteries allows for the detection of noncalcified plaques. In vivo volumetry of noncalcified plaques is feasible.

Classification of left main coronary obstruction--feasibility of surgical angioplasty and survival after coronary artery bypass surgery.

Angiographies of 384 patients who had coronary artery bypass surgery because of left main coronary artery (LMCA) obstruction during 1970-1989 were reviewed by analysing the pathology, feasibility of surgical angioplasty and survival. Complete LMCA occlusion was found in 2%, proximal ostial stenosis in 9%, mid-shaft stenosis in 24%, circular stenosis in 25% and distal bifurcation stenosis in 40% of the patients. Patients with an ostial stenosis were younger, more often women with less coronary artery disease and less calcified obstructions. Surgical angioplasty could have been an option in 22% of the patients. Early mortality was higher in patients with (4.7%) than in those without (1.9%) LMCA obstruction. The relative risk (RR) of early death was 1.9 (95% CL 1.1-3.5) after adjustment for patient characteristics. Similarly, the RR at 10 years was 1.3 (95% CL 1.0-1.6). LMCA obstruction was associated with an early and long-term increased mortality after surgery compared to patients without LMCA obstruction.

Feasibility to detect severe coronary artery stenoses with upright treadmill exercise magnetic resonance imaging.

We performed treadmill exercise magnetic resonance imaging in 27 patients with exertional chest pain who were referred for contrast coronary angiography to determine the feasibility of this method to identify severe coronary artery stenoses. The sensitivity and specificity for detecting >70% coronary artery luminal diameter narrowings on contrast coronary angiography were 79% and 85%, respectively.

Significance of exercise-induced ST changes in leads aVR, V5, and V1. Discrimination of patients with single- or multivessel coronary artery disease.

BACKGROUND: It is known that exercise-induced ST-segment elevation in lead V1 (V1-E) detects left anterior descending (LAD) stenosis. It was also postulated that ST elevation in aVR and simultaneous ST depression in V5 (aVR-E + V5-D) is a marker of ischemia due to significant stenosis of the LAD in patients with single-vessel disease. HYPOTHESIS: This study was undertaken to investigate the significance of the concomitant appearance of both electrocardiographic (ECG) ischemic markers, and of each of them alone during exercise, to detect either LAD stenosis as single-vessel coronary artery disease (CAD), or multivessel CAD involving LAD stenosis. METHODS: A total of 196 consecutive patients (152 men and 44 women, mean age 54 +/- 7 years) with at least one of these ECG markers, who underwent treadmill exercise testing with the Bruce protocol and coronary arteriography, were studied. RESULTS: Patients were divided into three groups. In Group A (83 patients with V1-E + aVR-E & V5-D), 93% of patients with single-vessel disease had significant LAD stenosis (p<0.001), whereas 75% of patients with double-vessel disease had significant stenoses of the LAD and the left circumflex (LCx) coronary arteries (p<0.01). In Group B (97 patients with aVR-E & V5-D but without V1-E), 43% of patients with single-vessel disease had significant LAD stenosis (p<0.08), whereas 85% of patients with double-vessel disease had significant stenoses of the LAD and the right coronary artery (RCA) (p<0.01). In Group C (16 patients with only V1-E), 60% of patients with single-vessel disease had significant LAD stenosis (p<0.05), whereas 75% of patients with double-vessel disease had significant LAD and LCx stenoses (p<0.05). CONCLUSIONS: The concomitant appearance of exercise-induced ST elevation in lead V1, ST elevation in lead aVR, and ST depression in lead V5, as well as the isolated appearance of ST elevation in lead V1 detect significant LAD stenosis as single-vessel disease, or significant stenoses of LAD and LCx arteries in patients with double-vessel disease, whereas the appearance of ST elevation in aVR & ST depression in V5 but without ST elevation in V1 correlates strongly with significant LAD and RCA stenoses and usually indicates double-vessel disease.