L. R. Smith

Continuing evolution of therapy for coronary artery disease : initial results from the era of coronary angioplasty

BACKGROUND Survival after coronary artery bypass graft surgery (CABG) and medical therapy in patients with coronary artery disease (CAD) has been studied in both randomized trials and observational treatment comparisons. Over the past decade, the use of coronary angioplasty (PTCA) has increased dramatically, without guidance from either randomized trials or prospective observational comparisons. The purpose of this study was to describe the survival experience of a large prospective cohort of CAD patients treated with medicine, PTCA, or CABG. METHODS AND RESULTS The study was designed as a prospective nonrandomized treatment comparison in the setting of an academic medical center (tertiary care). Subjects were 9263 patients with symptomatic CAD referred for cardiac catheterization (1984 through 1990). Patients with prior PTCA or CABG, valvular or congenital disease, nonischemic cardiomyopathy, or significant (> or = 75%) left main disease were excluded. Baseline clinical, laboratory, and catheterization data were collected prospectively in the Duke Cardiovascular Disease Databank. All patients were contacted at 6 months, 1 year, and annually thereafter (follow-up 97% complete). Cardiovascular death was the primary end point. Of this cohort, 2788 patients were treated with PTCA (2626 within 60 days) and 3422 with CABG (3080 within 60 days). Repeat or crossover revascularization procedures were counted as part of the initial treatment strategy. Kaplan-Meier survival curves (both unadjusted and adjusted for all known imbalances in baseline prognostic factors) were used to examine absolute survival differences, and treatment pair hazard ratios from the Cox model were used to summarize average relative survival benefits. For the latter, a 13-level CAD prognostic index was used to examine the relation between survival and revascularization as a function of CAD severity. The effects of revascularization on survival depended on the extent of CAD. For the least severe forms of CAD (ie, one-vessel disease), there were no survival advantages out to 5 years for revascularization over medical therapy. For intermediate levels of CAD (ie, two-vessel disease), revascularization was associated with higher survival rates than medical therapy. For less severe forms of two-vessel disease, PTCA had a small advantage over CABG, whereas for the most severe form of two-vessel disease (with a critical lesion of the proximal left anterior descending artery), CABG was superior. For the most severe forms of CAD (ie, three-vessel disease), CABG provided a consistent survival advantage over medicine. PTCA appeared prognostically equivalent to medicine in these patients, but the number of PTCA patients in this subgroup was low. CONCLUSIONS In this first large-scale, prospective observational treatment comparison of PTCA, CABG, and medicine, we confirmed the previously reported survival advantages for CABG over medical therapy for three-vessel disease and severe two-vessel disease. For less severe CAD, the primary treatment choices are between medicine and PTCA. In these patients, there is a trend for a relative survival advantage with PTCA, although absolute survival differences were modest. In this setting, treatment decisions should be based not only on survival differences but also on symptom relief, quality of life outcomes, and patient preferences.

Quantitative coronary arteriography

The effect of optimal medical therapy on coronary arterial anatomy was evaluated in 25 patients with unstable angina pectoris. Coronary arterial diameter and the extent of stenosis were exactly quantified in two successive coronary angiograms performed in each patient at approximately a 1 year interval (range 4 to 31 months, average 12.4 months). The measuring device was a vernier caliper with an accuracy of 0.05 mm. After 1 year of medical treatment 69 stenoses of the three major coronary branches showed no significant change: The average degree of area obstruction of 27 stenoses of the right coronary artery was 79 and 64 percent in the initial and second studies, respectively; that of 26 stenoses of the left anterior descending artery 76 and 77 percent, respectively, and that of 16 stenoses of the left circumflex artery 73 and 83 percent, respectively. In 11 patients, 14 stenoses showed a distinct progression of more than 20 percent area obstruction. All six stenoses showing more than 90 percent obstruction in the first angiogram progressed to complete obstruction within 1 year. In five other patients area obstruction in five stenoses regressed by more than 20 percent. The anatomy of vessel segments distal to obstructions remained unchanged within 1 year. It is concluded from these quantitative measurements that the distribution and severity of coronary lesions are similar in patients with stable and unstable angina pectoris. Coronary anatomy showed no significant change after 1 year of medical treatment. The rate of progression was substantially lower than previously reported in patients with stable angina pectoris.

Jugular bulb saturation and cognitive dysfunction after cardiopulmonary bypass

Inadequate cerebral oxygenation during cardiopulmonary bypass may lead to postoperative cognitive dysfunction in patients undergoing cardiac operations. A psychological test battery was administered to 255 patients before cardiac operation and just before hospital discharge. Postoperative impairment was defined as a decline of more than one standard deviation in 20% of tests. Variables significantly (p < 0.05) associated with postoperative cognitive impairment are baseline psychometric scores, largest arterial-venous oxygen difference, and years of education. Jugular bulb hemoglobin saturation is significant if it replaces arterial-venous oxygen difference in the model. Factors correlated with jugular bulb saturation at normothermia were cerebral metabolic rate of oxygen consumption (r = -0.6; p < 0.0005), cerebral blood flow (r = 0.4; p < 0.0005), oxygen delivery (r = 0.4; p < 0.0005), and mean arterial pressure (r = 0.15; p < 0.05). Three measures were significantly related to desaturation at normothermia and at hypothermia as well: greater cerebral oxygen extraction, greater arterial-venous oxygen difference, and lower ratio of cerebral blood flow to arterial-venous oxygen difference. We conclude that cerebral venous desaturation occurs during cardiopulmonary bypass in 17% to 23% of people and is associated with impaired postoperative cognitive test performance.

Factors and Their Influence on Regional Cerebral Blood Flow during Nonpulsatile Cardiopulmonary Bypass

Abstract In this study we examined the relationship of regional cerebral blood flow (CBF) to mean arterial pressure, systemic blood flow, partial pressure of arterial carbon dioxide (PaCO 2 ), nasopharyngeal temperature, and hemoglobin during hypothermic nonpulsatile cardiopulmonary bypass (CPB). Regional CBF was determined by clearance of xenon 133 in 67 patients undergoing coronary bypass grafting procedures. There was a significant decrease in regional CBF (55% decrease) during CPB, with nasopharyngeal temperature and PaCO 2 being the only two significant factors ( p 2 did not significantly affect regional CBF. We conclude that cerebral autoregulation is retained during hypothermic CPB. Under the usual conditions of CPB, variations in flow and pressure are not associated with important physiological or detrimental clinical affects.

Predictors of cognitive decline after cardiac operation

Despite major advances in cardiopulmonary bypass technology, surgical techniques, and anesthesia management, central nervous system complications remain a common problem after cardiopulmonary bypass. The etiology of neuropsychologic dysfunction after cardiopulmonary bypass remains unresolved and is probably multifactorial. Demographic predictors of cognitive decline include age and years of education; perioperative factors including number of cerebral emboli, temperature, mean arterial pressure, and jugular bulb oxygen saturation have varying predictive power. Recent data suggest a genetic predisposition for cognitive decline after cardiac surgery in patients possessing the apolipoprotein E epsilon-4 allele, known to be associated with late-onset and sporadic forms of Alzheimers disease. Predicting patients at risk for cognitive decline allows the possibility of many important interventions. Predictive power and weapons to reduce cellular injury associated with neurologic insults lend hope of a future ability to markedly decrease the impact of cardiopulmonary bypass on short-term and long-term neurologic, cognitive, and quality-of-life outcomes.

Regional blood flow during isoflurane and halothane anesthesia.

Cardiac output distribution and regional blood flow in 18 dogs during isoflurane and halothane anesthesia were studied in dose-related fashion. Surgical preparation consisted of left thoracotomy and placement of catheters in the left atrium and aorta through a femoral artery. Regional blood flow was studied one week after surgical preparation using a microsphere technique at the three stages: awake, 1 MAC, and 2 MAC of inhalation anesthesia. At each stage of the experiment, two sets of microspheres (15-and 9-μm diameter), labeled with different isotopes, were used simultaneously. Both anesthetics increased cerebral blood flow, decreased blood flow through preportal area, and preserved renal blood flow. Isoflurane increased hepatic artery blood flow at both levels of anesthesia, while halothane preserved the flow during 1 MAC and decreased it at 2 MAC. Apparently, isoflurane provided better oxygenation to the liver than halothane. Myocardial blood flow was increased during isoflurane (despite decrease in blood pressure and cardiac output) and decreased during halothane anesthesia. Isoflurane appears to be a coronary vasodilator with potential beneficial (improvement in myocardial blood supply) as well as hazardous (“steal effect”) effects on the heart.

Management and long-term outcome of aortic dissection.

All 163 patients admitted to one institution between 1975 and 1988 with aortic dissection were reviewed. Type I and type II patients received grafting of the ascending aorta, with an intraoperative mortality rate of 11%. For type III dissection, management was medical in 53 patients, while 19 required surgery for aortic rupture or expansion, with an intraoperative mortality rate of 11%. The 9- or 10-year survival rates were 29%, 46%, and 29% for types I, II, and III respectively. Of 135 patients with primary aortic dissection, 17 (13%) required subsequent aortic surgery. Cause of late death was other cardiovascular disease in 38%, rupture of another aortic segment in 18%, sudden death in 24%, and other medical conditions in 21%. Although operative therapy for types I and II dissections and reserving operation for selected type III dissections provides acceptable long-term survival, careful follow-up is necessary due to concurrent cardiovascular disease and residual aortic disease.

Pathogenesis of paroxysmal hypertension developing during and after coronary bypass surgery: A study of hemodynamic and humoral factors

A prospective study of hypertension first appearing during and after saphenous vein bypass coronary surgery was performed in 28 patients to examine the incidence, hemodynamics and mechanism of this problem. In 15 patients (54 percent) new hypertension developed (mean arterial pressure greater than 107 mm Hg), characterized by increased peripheral vascular resistance and unchanged cardiac output within 1 hour after surgery. These 15 patients had a longer history of angina of greater severity, but also had relatively well preserved ventricular myocardium. Because plasma renin activity was depressed in patients in the hypertensive group, activation of the renin-angiotensin system was not important in the pathogenesis of this postoperative hypertension. The expected decrease in total peripheral resistance at the onset of cardiopulmonary bypass was observed in all patients, but later during bypass the peripheral resistance increased in all patients in association with a rise in plasma epinephrine levels. Patients who had hypertension postoperatively had a greater increase in arterial pressure and total peripheral resistance during cardiopulmonary bypass than did those with normal postoperative blood pressure. An elevation in plasma epinephrine and norepinephrine concentration, suggesting enhanced sympathoadrenal responsiveness to the challenge of cardiopulmonary bypass, was characteristic of the hypertensive group. This evidence of enhanced sympathetic activity during surgery may be a useful predictor of the development of postoperative hypertension.

Liver circulation and function during isoflurane and halothane anesthesia.

Hepatic arterial blood flow (HABF) and portal blood flow (PBF) were measured in 18 dogs while awake and during isoflurane and halothane anesthesia. Surgical preparation 1 week before the measurements consisted of a left thoracotomy, placement of a left atrial catheter, and insertion of another catheter into the distal aorta via the left femoral artery. Cardiac output and liver blood flow were determined using microspheres at three stages: stage 1—awake state; stage 2—after 45 min of 1 MAC of isoflurane (eight dogs) or halothane (10 dogs) anesthesia; and stage 3—after 45 min of 2 MAC of inhalation anesthesia. Half-life and fractional clearance for indocyanine green (ICG) were determined 1 day before the experiment (awake state), and at the end of stages 2 and 3. Mean arterial pressure (MAP) and cardiac index (CI), as well as PBF, decreased during isoflurane and halothane anesthesia. HABF increased significantly during isoflurane anesthesia, remained unchanged during 1 MAC of halothane anesthesia, and significantly decreased during 2 MAC of halothane anesthesia. Apparently, hepatic oxygen supply was maintained much better during isoflurane than during halothane anesthesia. PBF correlated with CI during halothane (r = 0.97) and, to a certain extent, with MAP during isoflurane (r = 0.66). HABF correlated with CI and MAP during halothane (r = 0.74 and 0.71, respectively) but did not correlate with systemic hemodynamic variables during isoflurane. ICG half-life significantly increased during 1 and 2 MAC of halothane anesthesia. The degree of increase did not correlate with the level of anesthesia or the decrease in total hepatic blood flow. Isoflurane anesthesia was not accompanied by significant changes in ICG half-life. The data suggest that halothane has a more deleterious effect on liver blood flow than does isoflurane and, in addition, interferes with liver cell ability to absorb and excrete ICG.

Hemodynamic responses to anesthetic induction with midazolam or diazepam in patients with ischemic heart disease.

Hemodynamic responses to induction of anesthesia with midazolam maleate and diazepam were compared in patients with ischemic heart disease. While breathing 100% oxygen, 10 patients (group M) received midazolam maleate, 0.2 mg/kg, and 10 patients (group D) received diazepam, 0.5 mg/kg. In addition, 10 patients (group MN) breathing 50% nitrous oxide in oxygen received midazolam, 0.2 mg/kg. Patients in group M had a small but statistically significant (p < 0.05) decrease (vs awake control values) in systemic and pulmonary arterial blood pressure, pulmonary arterial occluded pressure, stroke index, and left and right ventricular stroke work indices. Patients in group D experienced statistically significant decreases in systemic blood pressure. The only statistically significant differences between groups M and D occurred 5 minutes following drug administration: heart rates were higher and systemic pressures and left ventricular stroke work indices were lower following midazolam. Hemodynamic changes following midazolam and nitrous oxide were similar to those observed in patients given midazolam and 100% oxygen. Patients in all three groups responded to endotracheal intubation with transient increases in blood pressure, heart rate, and systemic vascular resistance, but the hemodynamic values spontaneously returned toward control levels within 2 to 5 minutes. Although differing somewhat, midazolam, like diazepam, provided rapid, hemodynamically stable induction of anesthesia in patients with ischemic heart disease.