Assessing the cost of a cardiology residency program with a cost construction model.

BACKGROUND: Although the total costs of graduate medical education are difficult to quantify, this information is of great importance in planning over the next decade. METHODS AND RESULTS: A cost construction model was used to quantify the costs of teaching faculty, cardiology fellows' salaries and benefits, overhead (physical plant, equipment, and support staff), and other costs associated with the cardiology residency program at the University of Texas-Houston during the 1996 to 1997 academic year. Surveys of cardiology faculty and fellows, checked by the program director, were conducted to determine the time spent in teaching activities; access to institutional and departmental financial records was obtained to quantify associated costs. The model was then developed and examined for a range of assumptions concerning cardiology fellows' productivity, replacement costs, and the cost allocation of activities jointly producing clinical care and education. The instructional cost of training (cost of didactic, direct clinical supervision, preparation for teaching, and teaching-related administration, plus the support of the teaching program) was estimated at $73,939 per cardiology fellow per year. This cost was less than the estimated replacement value of the teaching and clinical services provided by cardiology fellows, $100,937 per cardiology fellow per year. Sensitivity analysis, with different assumptions on cardiology fellows' productivity and replacement costs, varied the cost estimates but generally represented the cardiology residency program as an asset. CONCLUSIONS: Cost construction models can be used as a tool to estimate variations in resource requirements resulting from changes in curriculum or educators' costs. In this residency, the value of the teaching and clinical services provided by cardiology fellows exceeded the cost of the resources used in the educational program.

Major histocompatibility complex class II antigen expression in rejecting cardiac allografts: detection using in vivo imaging with radiolabeled monoclonal antibody.

BACKGROUND: Increased expression of major histocompatibility complex class II (MHC-II) antigen occurs during cardiac allograft rejection. We tested the hypotheses that (1) radiolabeled antibody to MHC-II antigen allows detection of cardiac allograft rejection using nuclear imaging techniques and (2) uptake of radiolabeled antibody to MHC-II antigen correlates with severity of rejection. METHODS AND RESULTS: Thirteen beagles with cervical cardiac allografts were studied for 64+/-23 days by use of myocardial biopsy and in vivo imaging. Uptake of radiolabeled (131I [n=2], 123I [n=1], or 111In [n=10]) antibody to MHC-II increased over baseline in 7 animals that developed histological evidence of progressively worsening allograft rejection (group A), from 72.2+/-46.1 to 176.8+/-102.0 counts/pixel/mCi (P<.009). In 4 beagles without progressively worsening allograft rejection (group B), uptake was unchanged during follow-up (74.4+/-43.8 and 60.2+/-37.4 counts/pixel/mCi; P=NS). In animals studied with 111In-labeled antibody, uptake increased from 102.9+/-23.1 at baseline to 233.2+/-82.7 counts/pixel/mCi at follow-up in group A animals (P=.036), with no significant change in group B (91.1+/-34.9 and 75.9+/-24.9 counts/pixel/mCi; P=NS). Uptake of 111In-labeled antibody was 107.5+/-35.7, 135.9+/-70.8, and 307.8+/-90.1 counts/pixel/mCi in biopsy samples showing evidence of mild, moderate, and severe rejection, respectively (P=.001). Biopsy samples showing mild, moderate, and intense MHC-II expression antibody uptake had uptakes of 92.6+/-36.3, 158.5+/-54.7, and 307.8+/-90.1 counts/pixel/mCi, respectively (P=.00004). CONCLUSIONS: Radiolabeled monoclonal antibodies to MHC-II antigen can detect cardiac allograft rejection in this large mammal model of cardiac allograft transplantation, and this technique may have a potential role in the detection of rejection in patients after cardiac transplantation.

Comparison of angioscopy, intravascular ultrasound imaging and quantitative coronary angiography in predicting clinical outcome after coronary intervention in high risk patients.

OBJECTIVES: The purpose of this study was to identify qualitative or quantitative variables present on angioscopy, intravascular ultrasound imaging or quantitative coronary arteriography that were associated with adverse clinical outcome after coronary intervention in high risk patients. BACKGROUND: Patients with acute coronary syndromes and complex lesion morphology on angiography are at increased risk for acute complications after coronary angioplasty. Newer devices that primarily remove atheroma have not improved outcome over that of balloon angioplasty. Intravascular imaging can accurately identify intraluminal and intramural histopathologic features not adequately visualized during coronary arteriography and may provide mechanistic insight into the pathogenesis of abrupt closure and restenosis. METHODS: Sixty high risk patients with unstable coronary syndromes and complex lesions on angiography underwent angioscopy (n = 40) and intravascular ultrasound imaging (n = 46) during interventional procedures. In 26 patients, both angioscopy and intravascular ultrasound were performed in the same lesion. All patients underwent off-line quantitative coronary arteriography. Coronary interventions included balloon (n = 21) and excimer laser (n = 4) angioplasty, directional (n = 19) and rotational (n = 6) atherectomy and stent implantation (n = 11). Patients were followed up for 1 year for objective evidence for recurrent ischemia. RESULTS: Patients whose clinical presentation included rest angina or acute myocardial infarction or who received thrombolytic therapy within 24 h of procedure were significantly more likely to experience recurrent ischemia after intervention. Plaque rupture or thrombus on preprocedure angioscopy or angioscopic thrombus after intervention were also significantly associated with adverse outcome. Qualitative or quantitative variables on angiography, intravascular ultrasound or off-line quantitative arteriography were not associated with recurrent ischemia on univariate analysis. Multivariate predictors of recurrent ischemia were plaque rupture on preprocedure angioscopy (p < 0.05, odds ratio [OR] 10.15) and angioscopic thrombus after intervention (p < 0.05, OR 7.26). CONCLUSIONS: Angioscopic plaque rupture and thrombus were independently associated with adverse outcome in patients with complex lesions after interventional procedures. These features were not identified by either angiography or intravascular ultrasound.

Abolition of cyclic flow variations in stenosed, endothelium-injured coronary arteries in nonhuman primates with a peptide fragment (VCL) derived from human plasma von Willebrand factor-glycoprotein Ib binding domain.

BACKGROUND: Platelets play an important role in the pathophysiology of acute coronary syndromes. The interaction between the platelet glycoprotein Ib receptor and von Willebrand factor is a critical event allowing platelet adhesion and aggregation and subsequent thrombus formation in vessels with high shear rates and damaged endothelium. Therefore, we tested the hypotheses that VCL, an antagonist of von Willebrand-glycoprotein Ib binding domain, (1) attenuates/abolishes cyclic flow variations in stenosed, endothelium-injured coronary arteries in nonhuman primates and (2) reduces botrocetin-induced platelet aggregation in vitro after intravenous in vivo administration. METHODS AND RESULTS: Cyclic flow variations were established in anesthetized, open-chest baboons (n = 18). The baboons were divided into three groups. One group (n = 8) received a bolus of VCL (4 mg/kg IV) followed by an infusion (6 mg.kg-1.h-1) for 90 minutes (schedule A). Another group (n = 6) received a 2-mg/kg bolus followed by an infusion of 3 mg.kg-1.h-1 for 90 minutes (schedule B). The third group received a placebo infusion of normal saline. Under dosing schedule A, cyclic flow variations were abolished in 7 of 8 baboons after 33 +/- 18 minutes and markedly attenuated in 1. The frequency of cyclic flow variations fell from 18 +/- 9.4 per hour during the control period to 1 +/- 2.5 per hour after VCL infusion, P < .002. After cessation of infusion, cyclic flow variations remained abolished in 5 of 7 animals for > 3 hours and returned in 2 of 7 after 2 to 2.5 hours. Under schedule B, cyclic flow variations were abolished in 3 of 6 baboons and markedly reduced in the remainder. The number of cyclic flow variations fell from 17 +/- 4.8 per hour during the control period to 5 +/- 4.9 per hour after the VCL infusion, P < .001. The cyclic flow variations returned spontaneously at 38 +/- 40 minutes under this dosing schedule. Placebo infusion of saline had no effect on cyclic flow frequency or severity. VCL administration was associated with slight prolongation in bleeding time and a reduction in botrocetin-induced platelet aggregation. The bleeding time increased from a control time of 88 +/- 32 to 276 +/- 204 seconds, P < .03, and from 142 +/- 28 to 176 +/- 36 seconds, P = .056, for schedules A and B, respectively. VCL decreased platelet aggregation in response to botrocetin (20 micrograms/mL), from a control value of 66 +/- 30.3 to 33 +/- 31.3 omega, P < .05, and from 64 +/- 23.5 to 46 +/- 15.8 omega, P = .006, for dosing schedules A and B, respectively. CONCLUSIONS: Therefore, administration of a peptide fragment corresponding to von Willebrand-glycoprotein Ib binding domain (1) is effective in abolishing cyclic flow variations in stenosed, endothelium-injured coronary arteries and (2) reduces platelet aggregation in vivo in response to botrocetin in nonhuman primates.

Pathogenesis and management of acute heart failure and cardiogenic shock: role of inotropic therapy.

Patients with acute heart failure or cardiogenic shock following myocardial infarction have a high mortality. The first priority is to salvage any remaining viable myocardium, either by thrombolytic agents or, if necessary, by coronary angioplasty. A mechanical cause for the heart failure or shock needs to be excluded. Thereafter, the optimal therapeutic regimen needs to be chosen on the basis of each patient's hemodynamic profile. Patients can be broadly classified into three groups: (1) patients with a high left ventricular filling pressure (> 18 mm Hg) and a cardiac index < 2.2 L/min/m2 but systolic arterial pressure > 100 mm Hg; (2) patients with a systolic arterial pressure < 90 mm Hg, left ventricular filling pressure > 18 mm Hg, and cardiac index < 2.2 L/min/m2; and (3) patients with an elevated right ventricular filling pressure (> 10 mm Hg) and cardiac index < 2.2 L/min/m2 and a systolic arterial pressure < 100 mm Hg. Patients in the first subset usually require the use of vasodilator therapy and/or dobutamine. The choice of inotropic agent in patients in the second hemodynamic subset depends on the degree of systemic hypotension; dopamine is usually preferred initially because it increases arterial pressure in addition to improving cardiac output. Once the systemic blood pressure has been stabilized, dobutamine can be substituted for superior augmentation of cardiac output and its additional beneficial effects on the left ventricular filling pressure. Norepinephrine may be indicated in cases of severe systemic hypotension. Patients in hemodynamic subset 3, ie, right ventricular infarction, are treated with volume expansion and dobutamine. Use of nonpharmacologic means of circulatory support, eg, intra-aortic balloon pump or left ventricular assist device may also be required in any of these subsets.

Radionuclide assessment of ventricular function and risk stratification after myocardial infarction.

Prognosis after acute myocardial infarction is determined primarily by left ventricular function and by the extent to which additional coronary obstructions jeopardize viable myocardium. Radionuclide ventriculography is well suited for noninvasive assessments of resting and exercise ventricular function after acute myocardial infarction. The prognostic importance of resting left ventricular function after acute myocardial infarction is well established. Several studies have reported the prognostic utility of submaximal exercise radionuclide ventriculography at the time of hospital discharge. Patients with globally depressed left ventricular function after acute myocardial infarction are at increased risk for cardiac death, while patients with normal resting ventricular function but abnormal function during exercise appear to be at risk for nonfatal ischemic events. The development of gated tomographic techniques and new radiopharmaceuticals will make available more accurate and detailed assessments of ventricular function and combined assessments of function and perfusion. These new developments require further investigation but appear to be promising new techniques with the potential for providing improved assessments of prognosis after acute myocardial infarction.

Regional cardiac adrenergic function using I-123 meta-iodobenzylguanidine tomographic imaging after acute myocardial infarction.

The effect of acute myocardial infarction (AMI) on regional cardiac adrenergic function was studied in 27 patients mean +/- standard deviation 10 +/- 4 days after AMI. Regional adrenergic function was evaluated noninvasively with I-123 meta-iodobenzylguanidine (MIBG) using a dedicated 3-detector tomograph. Four hours after its administration, there was reduced MIBG uptake in the region of infarction, 0.38 +/- 0.31 counts/pixel/mCi x 103 compared with 0.60 +/- 0.30 counts/pixel/mCi x 103 and 0.92 +/- 0.35 counts/pixel/mCi x 103 in the zones bordering and distant from the infarct area, respectively, p less than 0.001. In all patients, the area of reduced MIBG uptake after 4 hours was more extensive that the associated thallium-201 perfusion defect with defect scores of 52 +/- 22 and 23 +/- 18%, respectively, p less than 0.001. After anterior wall AMI, the 4-hour MIBG defect score was 70 +/- 13% and the degree of mismatch between myocardial perfusion and MIBG uptake was 30 +/- 9% compared with 39 +/- 17 and 21 +/- 17% after inferior AMI, p less than 0.001 and p = 0.016, respectively. The 4-hour MIBG defect score correlated inversely with the predischarge left ventricular ejection fraction, r = -0.73, p less than 0.001. Patients with ventricular arrhythmia of greater than or equal to 1 ventricular premature complexes per hour, paired ventricular premature complexes or ventricular tachycardia detected during the late hospital phase had higher 4-hour MIBG defect scores, 62.5 +/- 15.0%, than patients with no detectable complex ventricular ectopic activity and a ventricular premature complex frequency of less than 1 per hour, 44.6 +/- 23.4%, p = 0.036.(ABSTRACT TRUNCATED AT 250 WORDS)

Development and prospective application of quantitative 2-day stress-rest Tc-99m methoxy isobutyl isonitrile SPECT for the diagnosis of coronary artery disease.

The clinical diagnostic accuracy of 2-day stress/rest quantitative Technetium-99m (Tc-99m) methoxy-isobutyl-isonitrile (Tc-sestamibi) single photon emission computerized tomography (SPECT) was assessed in a validation population of 61 patients from two different sites using two different camera/computer systems. The study population was made up of 53 catheterized patients, 29 from Cedars-Sinai Medical Center (CSMC) and 24 from the University of Texas Southwestern Medical Center (UTSMC), and eight UTSMC patients with a less than 5% pre-test likelihood of coronary artery disease. Interpretation employed gender-specific normal limits developed in an additional 15 men and 8 women at CSMC with less than a 5% likelihood of significant coronary artery disease. The results from CSMC compared with those from UTSMC were not different from each other. The overall sensitivity for detection of patients with coronary artery disease (greater than or equal to 50% stenosis) was 94% (CSMC: 92%, UTSMC: 95%). Overall specificity in the five patients with normal coronary arteriograms was 80% (CSMC: 67%, UTSMC: 100%). The normalcy rate in patients with a low likelihood of coronary artery disease was 88%. Vessel sensitivity was 85% (CSMC: 84%, UTSMC: 85%), while vessel specificity was 71% (CSMC: 72%, UTSMC: 69%). There was also no significant difference in the sensitivities and specificities between male and female populations. In addition, the agreement with coronary angiography for assessment of disease extent (normal coronary arteriogram, single or multivessel disease) was 75% (kappa = 0.6 +/- 0.1). This study demonstrated that Tc-sestamibi SPECT by quantitative analysis is accurate for the detection and localization of coronary artery disease. Furthermore, the CSMC quantitative method was shown to provide similar diagnostic accuracy when applied to data acquired at a different site using a different camera/computer system.

An automated analysis technique for thallium images.

The use of stress thallium-201 scans in the non-invasive assessment of myocardial perfusion is well established, despite several reports of considerable inter-observer variability in the assessment of perfusion defects. By applying a simple statistical algorithm to a set of normal thallium images and using a well defined criterion of abnormality, the threshold of normality in these 'statistical images' was obtained for each of four projections. Subsequently a test set of images from both normal volunteers and patients with arteriographically documented coronary artery disease were reported using statistical images at four levels (70, 75, 80 and 85% of the mean of the hottest pixels) and standard thallium images viewed on the computer monitor in both colour and black and white. Significant reductions in the inter-observer disagreement and enhanced predictive accuracy in the detection of significant coronary artery disease were obtained using the statistical images. The technique described and assessed would permit the reporting of thallium scans at a preselected value of sensitivity and specificity depending on the requirements of the particular study. It could be readily implemented, after local validation, in any department performing thallium scans where the gamma camera is interfaced to a computer.

Sustained haemodynamic effects of felodipine in patients with chronic cardiac failure.

1. The efficacy of felodipine a new calcium channel blocker with selective vasodilator activity in the management of severe low output cardiac failure, secondary to coronary heart disease, was determined in 10 patients. 2. Haemodynamic measurements were made at rest and during dynamic exercise and left ventricular function was assessed by radionuclide ventriculography. 3. Significant increases in cardiac index, stroke volume index and ejection fraction were found particularly during exercise, both acutely and following 4 weeks administration of felodipine therapy. 4. Felodipine could well have a significant role in the long term management of the patient with chronic cardiac failure.

Gated thallium scintigraphy in patients with coronary artery disease: an improved planar imaging technique.

The use of thallium scanning in the assessment of myocardial perfusion is well established. However, myocardial contraction leads to significant blurring of standard static images. By using electrocardiographic gating and a high sensitivity collimator, multiple view gated scans can be acquired prior to thallium redistribution. Reporting of these images on cine loop display in 100 consecutive patients undergoing coronary arteriography and 14 volunteers results in improved visual assessment of regional myocardial perfusion (with reduced interobserver variability) and, in addition, yields useful and accurate information on left ventricular function. The combination of better assessment of perfusion and information on wall motion results in improved detection of patients with significant coronary disease with no loss of specificity when compared with static images. Predictive accuracy improves from 85% to 94% with gated imaging. Gated thallium scanning could be readily applied in most centres using thallium at no extra cost and with improved predictive accuracy in the non-invasive detection of significant coronary disease.

A comparison of intravenous elantan and frusemide in patients with chronic cardiac failure.

Opiates and loop diuretics are the mainstay of treatment of acute pulmonary oedema, but it is now recognized that immediate response to intravenous loop diuretics is acute vasoconstriction with impaired cardiac performance. It therefore seemed appropriate to compare the effects of intravenous isosorbide 5-mononitrate and frusemide on systemic and coronary haemodynamics in a group of patients with chronic cardiac failure at cardiac catheterization. Intra-arterial blood pressure was recorded from the ascending aorta, pulmonary capillary wedge pressure and cardiac output were measured using a Swan-Ganz thermodilution catheter. Coronary venous blood flow was measured using a thermodilution technique and A-V oxygen difference across the myocardium was obtained from simultaneous blood sampling in the aorta and coronary sinus. Absolute myocardial nutrient blood flow was measured using a 133Xe clearance technique. Frusemide in a dosage of 0.5 mg/kg given intravenously provoked acute vasoconstriction with falls in cardiac output and stroke volume. Pulmonary capillary wedge pressure was unchanged in the first 60 min after administration of frusemide. Isosorbide 5-mononitrate in a dosage of 15 mg intravenously, significantly reduced the pulmonary capillary wedge pressure within 5 min, and with the subsequent fall in systolic arterial blood pressure, cardiac output was maintained. These results suggest that intravenous isosorbide 5-mononitrate could well be of value in the immediate management of the patient with acute pulmonary oedema.

Calcium channel blocker and isosorbide 5-mononitrate in the management of chronic cardiac failure.

In the management of the patient with chronic cardiac failure, the combination of an arteriolar vasodilator and venodilator should be beneficial. 8 patients with NYHA grade III-IV chronic cardiac failure were studied following placebo, after 4 weeks' therapy with the arteriolar vasodilator felodipine, and with the combination of felodipine and oral isosorbide 5-mononitrate. Haemodynamic measurements were made at rest and during dynamic exercise at an individual, fixed, near maximal workload. Ejection fraction (EF) was obtained by gated radionuclide ventriculography. At rest, heart rate was unchanged 73 +/- 6 at control, 72 +/- 4 with felodipine and 74 +/- 4 beats/min with the addition of isosorbide 5-mononitrate. Mean arterial pressure fell from 98 +/- 5 to 84 +/- 4 (p less than 0.02) and 84 +/- 3 mm Hg (p less than 0.02) with nitrate. Cardiac index increased from 2.2 +/- 0.1 to 2.5 +/- 0.2 litres/min/m2 with felodipine and further to 2.6 +/- 0.2 litres/min/m2 (p less than 0.02) with nitrate. Exercise tachycardia and mean arterial pressure were not significantly affected by therapy. Cardiac index increased on exercise from 4.4 +/- 0.3 to 4.8 +/- 0.3 litres/min/m2 with felodipine and 4.9 +/- 0.3 litres/min/m2 (p less than 0.05) with the addition of nitrate. Stroke volume index increased from 35.4 +/- 4 to 40.8 +/- 4 beats/min/m2 and further to 41.0 +/- 4 beats/min/m2 (p less than 0.05) and EF from 14 +/- 3 to 18 +/- 3% with nitrate. In conclusion, in patients with chronic cardiac failure, treatment with a calcium channel blocker produced sustained haemodynamic improvement, particularly on exercise, and combination with nitrate produced further benefit.