Guy Friedrich

A clinical prediction rule for the diagnosis of coronary artery disease: validation, updating, and extension

AIMS The aim was to validate, update, and extend the Diamond-Forrester model for estimating the probability of obstructive coronary artery disease (CAD) in a contemporary cohort. METHODS AND RESULTS Prospectively collected data from 14 hospitals on patients with chest pain without a history of CAD and referred for conventional coronary angiography (CCA) were used. Primary outcome was obstructive CAD, defined as ≥ 50% stenosis in one or more vessels on CCA. The validity of the Diamond-Forrester model was assessed using calibration plots, calibration-in-the-large, and recalibration in logistic regression. The model was subsequently updated and extended by revising the predictive value of age, sex, and type of chest pain. Diagnostic performance was assessed by calculating the area under the receiver operating characteristic curve (c-statistic) and reclassification was determined. We included 2260 patients, of whom 1319 had obstructive CAD on CCA. Validation demonstrated an overestimation of the CAD probability, especially in women. The updated and extended models demonstrated a c-statistic of 0.79 (95% CI 0.77-0.81) and 0.82 (95% CI 0.80-0.84), respectively. Sixteen per cent of men and 64% of women were correctly reclassified. The predicted probability of obstructive CAD ranged from 10% for 50-year-old females with non-specific chest pain to 91% for 80-year-old males with typical chest pain. Predictions varied across hospitals due to differences in disease prevalence. CONCLUSION Our results suggest that the Diamond-Forrester model overestimates the probability of CAD especially in women. We updated the predictive effects of age, sex, type of chest pain, and hospital setting which improved model performance and we extended it to include patients of 70 years and older.

Effect of Intensive Versus Standard Lipid-Lowering Treatment With Atorvastatin on the Progression of Calcified Coronary Atherosclerosis Over 12 Months: A Multicenter, Randomized, Double-Blind Trial

Background— Recent clinical trials have suggested that intensive versus standard lipid-lowering therapy provides for additional benefit. Electron-beam computed tomography provides the opportunity to quantify the progression of coronary artery calcification (CAC) in serial measurements. Methods and Results— In a multicenter, randomized, double-blind trial, 471 patients (age 61±8 years) who had no history of coronary artery disease and no evidence of high-grade coronary stenoses (>50% diameter reduction) were randomized if they had ≥2 cardiovascular risk factors and moderate calcified coronary atherosclerosis as evidenced by a CAC score ≥30. Patients were assigned to receive 80 mg or 10 mg of atorvastatin per day over 12 months. Progression of CAC volume scores could be analyzed in 366 patients. After pretreatment with 10 mg of atorvastatin for 4 weeks, 12 months of study medication reduced LDL cholesterol from 106±22 to 87±33 mg/dL in the group randomized to receive 80 mg of atorvastatin (P<0.001), whereas levels remained stable in the group randomized to receive 10 mg (108±23 at baseline, 109±28 mg/dL at the end of the study, P=NS). The mean progression of CAC volume scores, corrected for the baseline CAC volume score, was 27% (95% CI 20.8% to 33.1%) in the 80-mg atorvastatin group and 25% (95% CI 19.1% to 30.8%) in the 10-mg atorvastatin group (P=0.65). CAC progression showed no relationship with on-treatment LDL cholesterol levels. Conclusions— We did not observe a relationship between on-treatment LDL cholesterol levels and the progression of calcified coronary atherosclerosis. Over a period of 12 months, intensive atorvastatin therapy was unable to attenuate CAC progression compared with standard atorvastatin therapy. The possibility remains that the time window was too short to demonstrate an effect.

Detection of intralesional calcium by intracoronary ultrasound depends on the histologic pattern

This study was designed to examine the accuracy of intravascular ultrasound in detecting different histologic types of calcium pattern in human coronary artery atherosclerotic lesions. Previous studies have shown that calcium deposits in atherosclerotic lesions may occur in various forms and that intravascular ultrasound is a sensitive technique to detect calcium in atherosclerotic lesions. However, there has been no distinction between varying image representations of calcium and different histologic patterns of intralesional calcific deposits. Calcific lesions have an important clinical impact on the outcome of intracoronary transcatheter therapy, and the varying types of calcium may also play a role in the guidance of intracoronary interventions. Fifty fresh coronary vessel segments were studied by intracoronary ultrasound imaging and the images compared with the corresponding histologic sections. With intracoronary ultrasound imaging, calcium was defined as bright echo with corresponding sharp edged shadowing in the distal field. Three different histologic types of calcification were defined, and the sensitivity and specificity of the detection by intravascular ultrasound were determined for each type. Dense calcified plaques (type 1) were found 18 cases, microcalcification (small flecks of calcium) with single calcium fleck size < or = 0.05 mm (type 2) in 12 cases, and combination of calcified plaque surrounded by small calcium flecks (type 3) in 3 cases. In 17 (34%) coronary vessel segments, histologic analyses detected no calcium. Intracoronary ultrasound correctly detected 16 (89%) of 18 cases of type 1 calcification, 2 (17%) of 12 type 2, and all 3 (100%) type 3. Sensitivity for detection of type 1 and 3 calcification was 90%, with specificity of 100%.(ABSTRACT TRUNCATED AT 250 WORDS)

Prediction model to estimate presence of coronary artery disease: Retrospective pooled analysis of existing cohorts

Objectives To develop prediction models that better estimate the pretest probability of coronary artery disease in low prevalence populations. Design Retrospective pooled analysis of individual patient data. Setting 18 hospitals in Europe and the United States. Participants Patients with stable chest pain without evidence for previous coronary artery disease, if they were referred for computed tomography (CT) based coronary angiography or catheter based coronary angiography (indicated as low and high prevalence settings, respectively). Main outcome measures Obstructive coronary artery disease (≥50% diameter stenosis in at least one vessel found on catheter based coronary angiography). Multiple imputation accounted for missing predictors and outcomes, exploiting strong correlation between the two angiography procedures. Predictive models included a basic model (age, sex, symptoms, and setting), clinical model (basic model factors and diabetes, hypertension, dyslipidaemia, and smoking), and extended model (clinical model factors and use of the CT based coronary calcium score). We assessed discrimination (c statistic), calibration, and continuous net reclassification improvement by cross validation for the four largest low prevalence datasets separately and the smaller remaining low prevalence datasets combined. Results We included 5677 patients (3283 men, 2394 women), of whom 1634 had obstructive coronary artery disease found on catheter based coronary angiography. All potential predictors were significantly associated with the presence of disease in univariable and multivariable analyses. The clinical model improved the prediction, compared with the basic model (cross validated c statistic improvement from 0.77 to 0.79, net reclassification improvement 35%); the coronary calcium score in the extended model was a major predictor (0.79 to 0.88, 102%). Calibration for low prevalence datasets was satisfactory. Conclusions Updated prediction models including age, sex, symptoms, and cardiovascular risk factors allow for accurate estimation of the pretest probability of coronary artery disease in low prevalence populations. Addition of coronary calcium scores to the prediction models improves the estimates.

Angiographically silent atherosclerosis detected by intravascular ultrasound in patients with familial hypercholesterolemia and familial combined hyperlipidemia: Correlation with high density lipoproteins

OBJECTIVES This study sought to evaluate the extent of atherosclerosis in coronary and iliac arteries in patients with heterozygous familial hypercholesterolemia or familial combined hyperlipidemia, using intravascular ultrasound imaging. BACKGROUND Intravascular ultrasound imaging provides cross-sectional tomographic views of the vessel wall and allows quantitative assessment of atherosclerosis. METHODS Forty-eight nonsmoking, asymptomatic patients with heterozygous familial hypercholesterolemia or familial combined hyperlipidemia underwent intravascular ultrasound imaging of the left anterior descending coronary, left main coronary and common iliac arteries. Angiography showed only minimal or no narrowing in these vessels. Intravascular ultrasound images obtained during catheter pullback underwent morphometric analysis. Plaque burden was expressed as the mean and maximal intimal index (ratio of plaque area and area within the internal elastic lamina) and as the percent of vessel surface covered by plaque. RESULTS Intravascular ultrasound detected plaque more frequently than angiography in the left anterior descending (80% vs. 29%, respectively), left main (44% vs. 16%) and iliac arteries (33% vs. 27%). Plaque burden was higher in the left anterior descending (mean intimal index [+/- SD] 0.25 +/- 0.16) than in the left main (0.11 +/- 0.16, p < 0.001) and iliac arteries (0.02 +/- 0.04, p < 0.001). Angiography detected lumen narrowing only in coronary arteries with a maximal intimal index > or = 0.42 (left anterior descending artery) and > or = 0.43 (left main artery). The area within the internal elastic lamina increased with plaque area in the left anterior descending (r = 0.82, p < 0.001) and left main arteries (r = 0.53, p < 0.001). By stepwise multiple regression analysis, the strongest predictor for plaque burden in the left anterior descending artery was the level of high density lipoprotein (HDL) cholesterol and total/HDL cholesterol ratio for the left main artery. CONCLUSIONS In patients with heterozygous familial hypercholesterolemia and familial combined hyperlipidemia, extensive coronary plaque is present despite minimal or no angiographic changes. Compensatory vessel enlargement and diffuse involvement with eccentric plaque may account for the lack of angiographic changes. Levels of HDL cholesterol and total/HDL cholesterol ratio are far more powerful predictors of coronary plaque burden than are low density lipoprotein cholesterol levels in these patients with early, asymptomatic disease.

Integrated Coronary Revascularization Percutaneous Coronary Intervention Plus Robotic Totally Endoscopic Coronary Artery Bypass

Background— Robotic totally endoscopic coronary artery bypass (TECAB) of the left anterior descending artery (LAD) coupled with percutaneous coronary intervention (PCI) of a second coronary artery has been investigated in patients with multivessel disease to provide a minimally invasive therapeutic option. Methods and Results— TECAB of the LAD was performed using the left internal mammary artery (LIMA). A second lesion was treated with PCI before surgery, simultaneously, or after surgery. Three-month angiographic follow-up was performed in all patients and was subject to independent review. A total of 27 patients requiring double vessel revascularization were treated at 7 centers. Eleven patients underwent PCI before surgery, 12 patients underwent PCI after surgery, and 4 patients underwent simultaneous surgical and percutaneous intervention. Ten patients (37%) were treated with bare metal stents, whereas 17 patients (63%) were treated with drug-eluting stents. Postoperative angiographic evaluation demonstrated an overall LIMA anastomotic patency of 96.3% and PCI vessel patency of 66.7%. There were no deaths or strokes. One patient experienced a perioperative myocardial infarction. Eight of 27 patients (29.6%) required reintervention, 1 LIMA anastomotic stenosis (3.7%), 3 after bare metal stent (30%), and 4 after drug-eluting stent placement (23.5%). Conclusions— Integrated revascularization treatment plans provide minimally invasive options for patients with multivessel coronary artery disease. This approach may be accomplished with no mortality, low perioperative morbidity, and excellent angiographic LIMA patency. The reintervention rate after PCI in this series was higher than that reported elsewhere and should be investigated further. The choice of suitable vessel, type of stent and timing of the treatment must be carefully considered before implementing this hybrid strategy.

Simultaneous Hybrid COronary Revascularization Using Totally Endoscopic Left Internal Mammary Artery Bypass Grafting and Placement of RapamycIN Eluting Stents in the SAme IntervenTIONal Session

Objectives: Hybrid coronary revascularization procedures apply minimally invasive coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) for treatment of multivessel coronary artery disease. For logistic reasons simultaneous procedures would be desirable. In a pilot study the feasibility of simultaneous robotic totally endoscopic CABG and PCI using drug eluting stents was assessed. Patients and Methods: Five patients were scheduled to undergo simultaneous combined coronary inter- vention. A left internal mammary artery bypass graft was placed to the left anterior descending artery (LAD) in a completely endoscopic fashion using the daVinciTM telemanipulation system. PCI was carried out in the surgical operating room with the GE OEC9800 mobile coronary angiography C-arm. Rapamycin coated Cypher™ stents were placed into stenotic non-LAD targets. Results: The procedure was feasible in 4 patients, one patient was converted to a double CABG operation. There were no significant postoperative clinical complications and patients were discharged from intensive care unit and the hospital after 19 (18–61) hours and 6 (5–7) days respectively. At 6 months postoperatively all patients are free from angina. Conclusion: We conclude that simultaneous robotic totally endoscopic left internal mammary artery to LAD placement and PCI to non-LAD targets using drug eluting stents is feasible in one session.

Diagnostic Performance of 64-Slice Computed Tomography in Evaluation of Coronary Artery Bypass Grafts

OBJECTIVE The purpose of this study was to compare the diagnostic accuracy of 64-slice CT with that of invasive angiography in the detection of greater than 50% graft stenosis within 2 weeks of coronary artery bypass grafting and to investigate the clinical value of 64-slice CT. SUBJECTS AND METHODS Forty-one patients (70 grafts, 46 arterial and 24 venous) underwent 64-slice CT a mean of 2.6 years after minimally invasive or conventional coronary artery bypass surgery. RESULTS All 70 grafts were assessable, and none of the grafts was excluded from analysis. For the detection of 50-90% graft stenosis, the sensitivity of CT was 75%, the specificity was 95%, the positive predictive value was 67%, and the negative predictive value was 97% (true disease prevalence, 8/70 grafts; 11%). Greater than 50% graft stenosis and occlusion pooled together (prevalence, 14/70; 20%) were detected with a sensitivity of 85%, specificity of 95%, positive predictive value of 80%, and negative predictive value of 96%. Vein graft disease was found in eight (42%) of 19 patent vein grafts (graft age, 15.6 +/- 2.3 years). The disease was nonobstructive in three (16%) of the 19 grafts. The course of the left internal mammary artery was median retrosternal (< 1 cm deep) in 33.3% of conventionally sutured grafts. CONCLUSION Sixty-four-slice CT angiography can be used for accurate exclusion of greater than 50% graft stenosis, but detection of distal anastomotic stenosis is limited, and the degree of stenosis can be overestimated. The advantages of CT, however, are that it is noninvasive, vein graft disease can be diagnosed at an early stage, and complementary evaluation of extracardiac anatomic features provides useful information before coronary artery bypass grafting is redone.

Quality of Life Improvement after Robotically Assisted Coronary Artery Bypass Grafting

Objectives: Coronary artery bypass grafting (CABG) is associated with long rehabilitation periods and slow quality of life (QOL) improvement. Totally endoscopic coronary artery bypass grafting (TECAB) can be performed using robotic technology and remote access perfusion. The aim of this study was to evaluate whether TECAB leads to accelerated QOL improvement as compared to standard CABG. Methods: We included 120 patients who had received robotically assisted CABG, 56 of whom were operated on using standard sternotomy. These patients were compared to 55 patients who underwent the TECAB procedure and to 9 TECAB patients who required conversion to conventional sternotomy. QOL evaluation was performed before the operation and 1, 3 and 6 months after the procedure using the SF-36 health survey and a standardized questionnaire. Results: All quality of life aspects improved significantly in all study patients. At 3 months, TECAB patients showed significantly better QOL scores related to bodily pain and physical health. Hospital stay and time to restoration of daily activities were significantly shorter. Converted patients experienced similar courses to sternotomy patients in terms of QOL. Conclusions: TECAB using robotic technology leads to improved physical health, shorter hospital stay and a more rapid restoration of daily activities. Conversion from TECAB to sternotomy does not lead to QOL impairment as compared to primary sternotomy.

Preliminary Experience with Minimally Invasive Coronary-Artery Bypass Surgery Combined with Coronary Angioplasty

To the Editor: Percutaneous transluminal coronary angioplasty (PTCA) and coronary-artery bypass grafting (CABG) are both known to be highly effective in the treatment of coronary disease.1,2 Many r...