Jerome F. Breen

Constrictive Pericarditis in 26 Patients With Histologically Normal Pericardial Thickness

Background—Traditionally, increased pericardial thickness has been considered an essential diagnostic feature of constrictive pericarditis. Although constriction with a normal-thickness pericardium has been demonstrated clinically by noninvasive imaging, the details of clinicopathological correlates have not been described. Methods and Results—A total of 143 patients with proven constriction underwent pericardiectomy at Mayo Clinic between 1993 and 1999. Their baseline characteristics, operative data, and pathological specimens were reviewed retrospectively. The pericardium was of normal thickness (≤2 mm) in 26 patients (18%; group 1) and was thickened (>2 mm) in 117 (82%; group 2). The most common causes of constriction in group 1 included previous cardiac surgery, chest irradiation, previous infarction, and idiopathic disease. There was little difference in symptoms and findings on physical examination between the 2 groups. Microscopically, no patient had an entirely normal pericardium. Histopathological abnormalities in group 1 were mild and focal, including fibrosis, inflammation, calcification, fibrin deposition, and focal noncaseating granulomas. Pericardiectomy was equally effective in relieving symptoms regardless of the presence or absence of increased thickness. Conclusions—Pericardial thickness was not increased in 18% of patients with surgically proven constrictive pericarditis, although the histopathological appearance was focally abnormal in all cases. When clinical, echocardiographic, or invasive hemodynamic features indicate constriction in patients with heart failure, pericardiectomy should not be denied on the basis of normal thickness as demonstrated by noninvasive imaging.

Noninvasive definition of anatomic coronary artery disease by ultrafast computed tomographic scanning: A quantitative pathologic comparison study

OBJECTIVES The aim of this study was to determine the relation between coronary artery calcification detected by ultrafast computed tomographic scanning and histopathologic coronary artery disease. BACKGROUND Recent studies suggest that discrete coronary artery calcification as visualized by ultrafast computed tomographic scanning may facilitate the noninvasive detection or estimation, or both, of the in situ extent of coronary disease. Such quantitative relations have not been established. METHODS Thirteen consecutive perfusion-fixed autopsy hearts (from eight male and five female patients aged 17 to 83 years) were scanned by ultrafast computed tomographic scanning in contiguous 3-mm tomographic sections. The major epicardial arteries were dissected free, positioned longitudinally and scanned again in cross section. Coronary artery calcification in a coronary segment was defined as the presence of one or more voxels with a computed tomographic density > 130 Hounsfield units. Each epicardial artery was sectioned longitudinally, stained and measured with a planimeter for quantification of cross-sectional and atherosclerotic plaque areas at 3-mm intervals, corresponding to the computed tomographic scans. A total of 522 paired coronary computed tomographic and histologic sections were studied. RESULTS Direct relations were found between ultrafast computed tomographic scanning coronary artery calcium burden and atherosclerotic plaque area and percent lumen area stenosis. However, the range for plaque area or percent lumen stenosis, or both, associated with a given calcium burden was broad. Three hundred thirty-one coronary segments showed no calcification by computed tomography. Although atherosclerotic disease was found in several corresponding pathologic specimens, > 97% of these noncalcified segments were associated with nonobstructive disease (< 75% area stenosis); if no calcification was determined in an entire coronary vessel, all corresponding coronary disease was found to be nonobstructive. To determine the relation between arterial calcification and any atheromatous disease, computed tomographic calcium burden for each segment was paired with the histologic absence or presence of disease. Ultrafast computed tomographic scanning had a sensitivity and specificity of 59% and 90% and a negative and positive predictive value of 65% and 87%, respectively. A direct correlation was found (r = 0.99) between total calcium burden calculated from tomographic scans of the heart as a whole and scans of the arteries obtained in cross section. CONCLUSIONS The detection of coronary calcification by ultrafast computed tomographic scanning is highly predictive of the presence of histopathologic coronary disease, but the use of this technique to define the extent of coronary disease may be limited. However, the absence of coronary calcification at any site is highly specific for the absence of obstructive disease.

Clinical Presentation, Investigation, and Management of Pulmonary Vein Stenosis Complicating Ablation for Atrial Fibrillation

Background—Although segmental or circumferential ablation is effective in eliminating pulmonary vein (PV)–mediated atrial fibrillation (AF), this procedure may be complicated by the occurrence of PV stenosis. Methods and Results—To establish the clinical presentation, diagnostic manifestations, and interventional management of PV stenosis, 23 patients with stenosis of 34 veins complicating ablation of AF were evaluated. Each patient became symptomatic 103±100 days after undergoing ablation. In 8 veins, the ablation producing the PV stenosis was a repeated procedure for continued AF. Nineteen patients presented with dyspnea on exertion, 7 with dyspnea at rest, 9 with cough, and 6 with chest pain. On multirow spiral computed tomography examination, the narrowest lumen of the affected PVs measured 3±2 mm compared with 13±3 mm at baseline (P≤0.001). The relative perfusion of affected lung segments on isotope scans was reduced to 4±3% of total perfusion compared with 22±10% in unaffected segments. At percutaneous intervention, these veins showed 80±13% stenosis, with a mean gradient of 12±5 mm Hg. This was significantly reduced to a residual stenosis of 9±8% (P≤0.001) and a residual gradient of 3±4 mm Hg (P≤0.001). Twenty veins were treated with balloon dilatation alone, whereas 14 veins were stented with standard 10-mm-diameter bare-metal stents. Although the symptomatic response was nearly immediate and impressive, 14 patients developed in-stent or in-segment restenosis, requiring repeated interventions in 13. Conclusions—Percutaneous intervention produces rapid and dramatic symptom relief in patients with highly symptomatic PV stenosis after radiofrequency ablation for AF. Nevertheless, alternative treatment methods will be required to decrease recurrent in-stent or in-segment restenosis.

Coronary Calcium, as Determined by Electron Beam Computed Tomography, and Coronary Disease on Arteriogram Effect of Patient’s Sex on Diagnosis

BACKGROUND Coronary artery calcium identified by electron beam computed tomography (EBCT) has potential for noninvasive localization of coronary atherosclerotic disease. However, the effect of a patients sex on its diagnostic capability has not been examined in a clinical population. METHODS AND RESULTS Fifty women and 89 men had EBCT scans done an average of 1 day after coronary arteriography. Maximum arteriographic percent luminal diameter stenosis of any artery was paired with the total EBCT coronary calcium score for each subject. The women (age, 56 +/- 11 years [mean +/- SD]) were older than the men (age, 47 +/- 7 years), but the subjects were matched for indications for arteriography and extent of disease as assessed by arteriography. Sensitivity, specificity, and positive and negative predictive values for coronary calcium were nearly identical for men and women, regardless of the degree of arteriographic disease. EBCT was highly sensitive to the presence of arteriographic disease (range, 94% to 100%), but had only moderate specificity (57% to 66%) for significant disease (> or = 50% stenosis) and low specificity (35% to 38%) for any arteriographic disease (> 0% stenosis). Negative predictive values in men and women ranged from 79% to 91% for any arteriographic disease and from 95% to 100% for significant disease, respectively. Numerical calcium scores were significantly different between subjects with normal arteriograms and those with significant disease; however, calcium score had limited power to separate trivial, moderate, and significant disease. Receiver operating characteristic curve areas, determined as an extension of the analyses of sensitivity and specificity, were high for EBCT-defined calcium scores for both any arteriographic disease and significant arteriographic disease, and were not different between the sexes. CONCLUSIONS In a middle-aged population, noninvasive definition of coronary calcium by EBCT has similar predictive value for arteriographic coronary artery disease in men and women.

Incidental Renal Artery Stenosis Among a Prospective Cohort of Hypertensive Patients Undergoing Coronary Angiography

OBJECTIVE To determine the feasibility, safety, and clinical yield of angiographic screening among hypertensive patients undergoing coronary angiography. PATIENTS AND METHODS This study was a prospective cohort analysis of hypertensive patients who underwent cardiac catheterization at a tertiary care referral center from July 1998 to March 1999. Abdominal aortography was performed to screen for renal artery stenosis, the percentage of which was measured. RESULTS The mean +/- SD age of the 297 study patients was 64.9+/-10.2 years; 58.6% were male, and 98.0% were white. Mean +/- SD systolic/diastolic blood pressure was 142.8+/-22.5/79.6+/-11.4 mm Hg. Aortography required a mean incremental dose of 62+/-9 mL of nonionic contrast agent. No complications were attributable to aortography. Of 680 renal arteries, 611 (90%) were visualized adequately. Also, 53% of patients had normal renal arteries, 28% had stenoses less than 50%, and 19.2% had stenoses of 50% or more. Renal artery stenosis was bilateral in 3.7% of patients and high grade (>70% stenosis) in 7%. Patients with renal artery stenosis were more likely to have had a previous coronary intervention. In multivariate analysis, systolic blood pressure (odds ratio [OR], 1.2; 95% confidence interval [CI], 1.03-138; P=.02), history of stroke or transient ischemic attack (OR, 2.7; 95% CI, 1.27-5.78; P=.01), and cancer (OR, 2.0; 95% CI, 1.02-3.82; P=.04) independently correlated with renal artery stenosis of 50% or more. CONCLUSION The prevalence of incidental renal artery stenosis among hypertensive patients undergoing coronary catheterization is significant. Therefore, screening abdominal aortography should be considered in these patients to better define their risk of cardiovascular complications.

Aprotinin for coronary bypass operations: Efficacy, safety, and influence on early saphenous vein graft patency. A multicenter, randomized, double- blind, placebo-controlled study

The purpose of this study was to evaluate the efficacy and safety of aprotinin in a U.S. population of patients undergoing coronary artery bypass grafting. Early vein graft patency rates were assessed by ultrafast computed tomography. A total of 216 patients at five centers were randomized to receive either high-dose aprotinin or placebo during the operation; 151 patients underwent primary operation, and 65 underwent repeat procedures. Total blood product exposures in the primary group were 2.2 per patient receiving aprotinin as compared with 5.7 per patient receiving placebo (p = 0.010). The repeat group had 0.3 exposures per patient receiving aprotinin as compared with 10.7 per patient receiving placebo (p = < 0.001). Consistent reductions in the percent of patients requiring donor red blood cells and in the number of units of platelets, fresh frozen plasma, and cryoprecipitate required were associated with the use of aprotinin in both primary and repeat groups. Mortality was 5.6% in the aprotinin group and 3.7% in the placebo group (p = 0.517). In the primary group, clinical diagnoses of myocardial infarction were made in 8.9% of patients receiving aprotinin as compared with 5.6% of the patients receiving placebo (p = 0.435). In the repeat group, infarctions occurred in 10.3% of patients receiving aprotinin and 8.3% of patients receiving placebo (p = 1.000). Secondary analysis of electrocardiograms and available enzyme data showed no significant difference in infarction rates between the treatment groups. There was no difference in clinically significant renal dysfunction. The early vein graft patency rates were 92.0% in the aprotinin group and 95.1% in the placebo group (p = 0.248). In this study, aprotinin was effective in reducing bleeding and blood product transfusion rates, and its use was not associated with an increase in complications. An adverse effect on early vein graft patency rates was not demonstrated, but the number of grafts assessed was insufficient for absolute conclusions in this regard.

Use of Electron-Beam Computed Tomography in the Evaluation of Chest Pain Patients in the Emergency Department

STUDY OBJECTIVE We sought to determine whether electron-beam computed tomography (EBCT) could be used as a triage tool in the emergency department for patients with angina-like chest pain, no known history of coronary disease, normal or indeterminate ECG findings, and normal initial cardiac enzyme concentrations. METHODS We conducted a prospective observational study of 105 patients admitted between December 1995 and October 1997 to the ED of a large tertiary care hospital with 70,000 annual ED visits. The study group was comprised of women aged 40 to 65 years and men aged 30 to 55 years who presented with angina-like chest pain requiring admission to the hospital or chest pain observation unit. All patients underwent EBCT of the coronary arteries, along with other cardiac testing as deemed necessary by staff physicians. RESULTS Of the 105 patients, 100 underwent other cardiac testing during hospitalization. Evaluation included treadmill exercise testing in 58, coronary angiography in 25, radionuclide stress testing in 19, and echocardiography in 11. Results of EBCT and cardiac testing were negative for both in 53 patients (53%), positive for both in 14 (14%), positive for tomography and negative for cardiac testing in 32 (32%), and negative for tomography and positive for cardiac testing in only 1 patient. This positive test result, on a treadmill exercise test, was ruled a false positive by an independent staff cardiologist. Two other female patients with normal exercise sestamibi or coronary angiography and EBCT findings also had false-positive treadmill exercise results. The sensitivity of EBCT was 100% (95% confidence interval, 77% to 100%), with a negative predictive value of 100% (95% confidence interval, 94% to 100%). Specificity was 63% (95% confidence interval, 54% to 75%). CONCLUSION EBCT is a rapid and efficient screening tool for patients admitted to the ED with angina-like chest pain, normal cardiac enzyme concentrations, indeterminate ECG findings, and no history of coronary artery disease. Our study suggests that patients with normal initial cardiac enzyme concentrations, normal or indeterminate ECG findings, and negative results on EBCT may be safely discharged from the ED without further testing or observation. Larger studies are required to confirm this conclusion.

Contrast echocardiography improves the accuracy and reproducibility of left ventricular remodeling measurements: A prospective, randomly assigned, blinded study

OBJECTIVES We sought to assess the impact of contrast injection and harmonic imaging, on the measure by echocardiography of left ventricular (LV) remodeling. BACKGROUND Left ventricular remodeling is a precursor of LV dysfunction, but the impact of contrast injection and harmonic imaging on the accuracy or reproducibility of echocardiography is unclear. METHODS We prospectively collected LV images by using simultaneous methods. Then, LV volumes were measured off-line, in blinded manner and in random order. The accuracy of echocardiography was determined in comparison to electron beam computed tomography (EBCT) in 26 patients. The reproducibility of echocardiography was assessed by three blinded observers with different training levels in 32 patients. RESULTS End-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV) and ejection fraction (EF), as measured by EBCT (195 +/- 55, 58 +/- 24 and 137 +/- 35 ml and 71 +/- 5%, respectively) and echocardiography with harmonic imaging and contrast injection (194 +/- 51, 55 +/- 20 and 140 +/- 35 ml and 72 +/- 4%, respectively), showed no differences (all p > 0.15) and excellent correlations (all r > 0.87). In contrast, echocardiography using harmonic imaging without contrast injection underestimated the EBCT results (all p < 0.01). Reproducibility was superior with rather than without contrast injection for intraobserver and interobserver variabilities (all p < 0.001). Values measured by different observers were different without contrast injection, but were similar with contrast injection (all p > 0.18). Consequently, intrinsic patient differences represented a larger and almost exclusive proportion of global variability with contrast injection for EDV (94 vs. 79%), ESV (93 vs. 82%), SV (87 vs. 53%) and EF (84 vs. 41%), as compared with harmonic imaging without contrast injection (all p < 0.005). CONCLUSIONS For assessment of LV remodeling, echocardiography with harmonic imaging and contrast injection improved the accuracy and reproducibility, as compared with imaging without contrast injection. With contrast injection, variability was almost exclusively due to intrinsic patient differences. Therefore, when evaluation of LV remodeling is deemed important, assessment after contrast injection should be the preferred echocardiographic approach.

Aortic Valve Calcification Determinants and Progression in the Population

Background—Aortic valve calcification (AVC) is considered degenerative. Recent data suggested links to atherosclerosis or coronary disease (CAD). Methods and Results—AVC and coronary artery calcifications (CAC) were prospectively assessed by Electron-Beam-Computed-Tomography in 262 population-based research participants ≥60 years. AVC was frequent (27%) with aging (P<0.01) and in men (P<0.05). AVC was associated with diabetes, hypertension, higher body-mass-index, and serum glucose (all P<0.05). AVC was a marker of higher prevalence (P<0.01) and severity of CAD (CAC score: 441±802 versus 265±566, P<0.05) independently of age. After follow-up of 3.8±0.9 years, AVC score increased (94±271 versus 54±173, P<0.01, +11±32 U/year), faster with higher baseline AVC score (P<0.01). Compared with participants remaining free of AVC, de novo acquisition of AVC was associated with higher LDL-cholesterol (141±31 versus 121±27 mg/dL, P<0.05) and faster CAC progression (+78±87 versus +28±47 U/year, P<0.05). In multivariate analysis, LDL-cholesterol independently determined AVC acquisition while higher baseline AVC scores determined faster progression of existing AVC. Conclusion—In the population, AVC is frequent with aging and atherosclerotic risk factors. AVC is a marker of subclinical CAD. AVC is progressive, appearing de novo with progressive atherosclerosis whereas established AVC progresses independently of atherosclerotic risk factors and faster with increasing initial AVC loads.

Coronary calcification by electron beam computed tomography and obstructive coronary artery disease: a model for costs and effectiveness of diagnosis as compared with conventional cardiac testing methods☆

OBJECTIVES The purpose of this study was to determine if electron beam computed tomography (EBCT) has potential as a cost-effective approach to diagnosis of obstructive coronary disease. BACKGROUND Coronary calcification quantified by EBCT is closely related to the extent of atherosclerosis. METHODS A model based upon published sensitivities (Se)/specificities (Sp) for diagnosis in an ambulatory patient of obstructive coronary disease (> or =50% stenosis) and population prevalence was tested for angiography alone, or treadmill exercise, stress echocardiography, stress thallium or predetermined EBCT calcium score outpoints, followed by angiography if indicated. RESULTS Total direct testing costs increased in proportion to disease prevalence whereas cost-effectiveness, direct costs/patient diagnosed correctly with disease, decreased as a function of prevalence. Using an EBCT calcium score of 168 (Se/Sp = 71%/90%) provided for the least costly and most cost-effective noninvasive pathway. Calcium scores of 80 (Se/Sp = 84%/84%) and 37 (Se/Sp = 90%/77%) were also cost-effective when prevalence of disease was < or =70%; but results for a >0 calcium score (Se/Sp = 95%/46%) cutpoint were not superior to conventional methods. Calcium score cutpoints of 37, 80 or 168 provided similar or superior overall negative and positive predictive values to conventional noninvasive testing pathways across all prevalence subgroups. CONCLUSIONS In ambulatory patients evaluated for obstructive coronary disease, a testing pathway utilizing quantification of coronary calcium by EBCT as an initial noninvasive testing approach minimized direct costs, and maximized cost-effectiveness in population groups with low/ moderate disease prevalence (< or =70%); as expected, direct angiography as the first and only test proved most cost-effective in patients with a high prevalence (>70%) of disease.