Aggressive cholesterol lowering delays saphenous vein graft atherosclerosis in women, the elderly, and patients with associated risk factors. NHLBI post coronary artery bypass graft clinical trial. Post CABG Trial Investigators.

BACKGROUND: The NHLBI Post Coronary Artery Bypass Graft trial (Post CABG) showed that aggressive compared with moderate lowering of low-density lipoprotein-cholesterol (LDL-C) decreased obstructive changes in saphenous vein grafts (SVGs) by 31%.1 Using lovastatin and cholestyramine when necessary, the annually determined mean LDL-C level ranged from 93 to 97 mg/dL in aggressively treated patients and from 132 to 136 mg/dL in the others (P<0.001). METHODS AND RESULTS: The present study evaluated the treatment effect in subgroups defined by age, gender, and selected coronary heart disease (CHD) risk factors, ie, smoking, hypertension, diabetes mellitus, high-density lipoprotein cholesterol (HDL-C) <35 mg/dL, and triglyceride serum levels >/=200 mg/dL at baseline. As evidenced by similar odds ratio estimates of progression (lumen diameter decrease >/=0.6 mm) and lack of interactions with treatment, a similar beneficial effect of aggressive lowering was observed in elderly and young patients, in women and men, in patients with and without smoking, hypertension, or diabetes mellitus, and those with and without borderline high-risk triglyceride serum levels. The change in minimum lumen diameter was in the same direction for all subgroup categories, without significant interactions with treatment. CONCLUSIONS: Aggressive LDL-C lowering delays progression of atherosclerosis in SVGs irrespective of gender, age, and certain risk factors for CHD.

Long-term effects on clinical outcomes of aggressive lowering of low-density lipoprotein cholesterol levels and low-dose anticoagulation in the post coronary artery bypass graft trial. Post CABG Investigators.

BACKGROUND: The Post Coronary Artery Bypass Graft Trial, designed to compare the effects of 2 lipid-lowering regimens and low-dose anticoagulation versus placebo on progression of atherosclerosis in saphenous vein grafts of patients who had had CABG surgery, demonstrated that aggressive lowering of LDL cholesterol (LDL-C) levels to <100 mg/dL compared with a moderate reduction to 132 to 136 mg/dL decreased the progression of atherosclerosis in grafts. Low-dose anticoagulation did not significantly affect progression. METHODS AND RESULTS: Approximately 3 years after the last trial visit, Clinical Center Coordinators contacted each patient by telephone to ascertain the occurrence of cardiovascular events and procedures. The National Death Index was used to ascertain vital status for patients who could not be contacted. Vital status was established for all but 3 of 1351 patients. Information on nonfatal events was available for 95% of surviving patients. A 30% reduction in revascularization procedures and 24% reduction in a composite clinical end point were observed in patients assigned to aggressive strategy compared with patients assigned to moderate strategy during 7.5 years of follow-up, P=0. 0006 and 0.001, respectively. Reductions of 35% in deaths and 31% in deaths or myocardial infarctions with low-dose anticoagulation compared with placebo were also observed, P=0.008 and 0.003, respectively. CONCLUSIONS: -The long-term clinical benefit observed during extended follow-up in patients assigned to the aggressive strategy is consistent with the angiographic findings of delayed atherosclerosis progression in grafts observed during the trial. The apparent long-term benefit of low-dose warfarin remains unexplained.

Effect of an aggressive lipid-lowering strategy on progression of atherosclerosis in the left main coronary artery from patients in the post coronary artery bypass graft trial.

BACKGROUND: The Post Coronary Artery Bypass Graft Trial, designed to compare the effects of two lipid-lowering regimens and low-dose anticoagulation versus placebo on progression of atherosclerosis in saphenous vein grafts of patients who had had CABG surgery, demonstrated that aggressive lowering of LDL cholesterol levels to a mean yearly cholesterol level from 93 to 97 mg/dL compared with a moderate reduction to a level of 132 to 136 mg/dL decreased the progression of atherosclerosis in saphenous vein grafts. Low-dose anticoagulation did not affect progression. This secondary analysis tested the hypothesis that a similar decrease in progression of atherosclerosis would also be present in native coronary arteries as measured in the left main coronary artery (LMCA). METHODS AND RESULTS: A sample of 402 patients was randomly selected from 1102 patients who had baseline and follow-up views of the LMCA suitable for analysis. Patients treated with the aggressive lipid-lowering strategy had less progression of atherosclerosis in the LMCA as measured by changes in minimum (P=0.0003) lumen diameter or the maximum percent stenosis (P=0.001), or the presence of substantial progression (P=0.008), or vascular occlusion (P=0.005) when compared with the moderate strategy. CONCLUSIONS: A strategy of aggressive lipid lowering results in significantly less atherosclerosis progression than a moderate approach in LMCAs.

The disease-free wall in coronary atherosclerosis: its relation to degree of obstruction.

Coronary atherosclerotic lesions are more often located eccentrically (70%) than concentrically (30%). In this study, the configuration of eccentric coronary artery atherosclerotic lesions was assessed by means of computerized planimetry in 100 specimens of eccentric arterial lesions. Special attention was given to the relation between the disease-free wall and the severity of obstruction. The mean disease-free wall are length measured between 17 and 23% of the total vessel circumference in eccentric coronary artery lesions that obstructed 50 to 90% of the cross-sectional area. This ratio persisted irrespective of the location of the lesion within the vessel and was not significantly different with vessels of different sizes. The presence of disease-free arcs of coronary artery wall as observed in this pathologic study may relate to three factors in clinical coronary artery disease: The published observations of spasm in segments of arteries harboring structural obstructive lesions may be explained by the frequent presence of uninvolved arcs of coronary artery walls. Multiple views during coronary arteriography are necessary to accurately reflect the degree of obstruction. The results of percutaneous transluminal coronary angioplasty may be influenced by both the disease-free arc and the atheromatous obstruction.

Adult cardiology and the expanding supply of physicians.

The number of cardiologists can be projected with considerable accuracy into the next century. The total cardiology pool of physicians will increase until the year 2015 at which time those entering and leaving the pool will come into equilibrium. At that time the ratio of active cardiologists to the population will have greatly increased. This nation's future need for cardiologists is difficult to assess with any degree of precision. Therefore, this is the time for updating practice profile studies. Such studies today could be formulated in a manner to provide more detailed information on the cardiologist's daily activities. In addition, a data base developed through methodology such as the consensus formation approach must be developed and updated on a periodic basis. Through such analyses it will be possible to quantitate the future needs of cardiovascular manpower.

Multifocal atrial tachycardia.

Multifocal atrial tachycardia (MAT) was observed in 41 patients, 35 of whom were in acute respiratory distress. A hospital mortality of 37% reflected the seriousness of their underlying conditions. In no patient was the arrhythmia the primary cause of death. The MAT preceded and/or followed atrial fibrillation (AF) or atrial flutter (Af) in 19 patients (46%). The MAT simulated AF in several cases in which P-waves were inconspicuous. Our cases suggest that MAT is not a manifestation of digitalis intoxication. Quinidine sulfate, procainamide hydrochloride, lidocaine, and phenytoin (diphenythydantoin) did not affect the rhythm. Digitalis was usually not effective in slowing the ventricular response in patients with MAT. Propranolol hydrochloride was given to seven patients and was effective in slowing the atrial rate in all cases. An attempt at electrocardioversion was unsuccessful in one patient.

Rupture of the spleen in infective endocarditis.

A patient had delayed spontaneous rupture of the spleen complicating infective endocarditis. In 20 other cases reported through 1973, the most common presentation was found to be left upper quadrant pain followed by signs of peritoneal irritation and cardiovascular collapse. Abdominal paracentesis consistently yields free blood or pus in the peritoneal cavity; blood replacement and emergency splenectomy may be lifesaving. The basic pathological mechanisms may be (1) rupture of a mycotic aneurysm into the splenic substance (2) rupture of a splenic abscess, and (3) rupture of a suppurating intrasplenic vessel with hematoma formation, subcapsular dissection, and delayed capsular tear.

The effect of aggressive and moderate lowering of LDL-cholesterol and low dose anticoagulation on plasma lipids, apolipoproteins and lipoprotein families in post coronary artery bypass graft trial.

The reported results (The Post Coronary Artery Bypass Graft Trial Investigators. The effect of aggressive lowering of low-density lipoprotein cholesterol levels and low-dose anticoagulation on obstructive changes in saphenous-vein coronary-artery bypass grafts. New Engl J Med 1997;336:153-162) of the Post Coronary Artery Bypass Graft (Post CABG) trial have shown that aggressive lowering was more effective than moderate lowering of low density lipoprotein (LDL) cholesterol in reducing the progression of atherosclerosis in saphenous-vein grafts (27 vs. 39%; P < 0.001); low dose warfarin had no effect on the progression of atherosclerosis. The present report describes the effect of long-term (an average of 4.3 years) aggressive treatment with high (40-80 mg/day) and moderate treatment with low (2.5-5 mg/day) doses of lovastatin on lipids, apolipoproteins (apo) and apoA- and apoB-containing lipoprotein families. To achieve the target LDL-cholesterol levels (60-85 mg/dl for aggressive group and 134-140 mg/dl for moderate group), cholestyramine (8 g/day) was given to 25% of subjects on aggressive and 5% of subjects on moderate treatment. Although with both treatment strategies there were significant decreases (P<0.001) in the levels of total cholesterol, LDL-cholesterol, apoB, LDL-apoB and cholesterol-rich Lp-B family, percent changes in the levels of these variables were greater in the aggressive- than in the moderate-treatment groups. These treatments had only marginal effects in increasing the levels of high density lipoprotein cholesterol, apoA-I and Lp-A-I and Lp-A-I:A-II families. The long-term aggressive treatment exerted no effect on the concentrations of triglycerides, apoC-IlI, apoC-III in VLDL + LDL and triglyceride-rich Lp-Bc families. Neither treatment affected the levels of Lp(a). The potentially modifying influence of warfarin and apoE phenotypes on lovastatin-induced changes in lipoprotein variables was found to be of little significance. It is likely that the beneficial effect of lovastatin in reducing the progression of atherosclerosis in grafts is mediated through its specific lowering effect on cholesterol-rich Lp-B particles.

Effects of sulfinpyrazone on early graft closure after myocardial revascularization.

The effect of sulfinpyrazone on the incidence of early postoperative closure of saphenous vein bypass grafts was compared with placebo in a prospective randomized study of 255 eligible patients. Treatment with sulfinpyrazone (800 mg/day) was started 24 hours after operation in 130 patients; 125 patients received placebo. Graft blood flow was measured at operation in 96 percent of all patients. Graft angiography was performed between the 7th and 14th postoperative days. There was no significant difference between the two groups in graft blood flow, number and diameter of the grafted arteries, left ventricular filling pressure or ejection fraction. During the study 73 patients (41 on sulfinpyrazone, 32 on placebo therapy) were excluded because graft angiography was contraindicated or because of concomitant use of anticoagulant or antiplatelet drugs. The incidence rate of early graft closure in the remaining 182 patients (43.1 grafts) was 3.8 percent (8 or 212) in the sulfinpyrazone group and 9.1 percent (20 of 219) in the placebo group (p less than 0.025). The incidence of graft closure for the sulfinpyrazone and placebo groups classified according to the recipient coronary arteries was: (1) left anterior descending artery; 3 of 98 versus 11 of 111; p less than 0.05; (2) left circumflex coronary artery: 3 of 50 versus 5 of 43; difference not significant; (3) right coronary artery: 2 of 64 versus 4 of 65; difference not significant. The incidence of closure in grafts with a flow of less than 30 ml/min did not differ significantly in the sulfinpyrazone and placebo groups (4 of 26 versus 6 of 22). These results suggest that sulfinpyrazone reduces the incidence of early graft closure in grafts with a flow rate greater than 30 ml/min.

Chest pain as a predictor of coronary artery disease in patients with obstructive aortic valve disease.

To clarify the association between chest pain and significant coronary artery disease in patients who have aortic valve disease, 76 consecutive candidates for aortic valve replacement were evaluated prospectively with use of a historical questionnaire and coronary arteriography. Of the 76 patients, 19 (25 percent) had no chest pain, 21 (28 percent) had chest pain that was not typical of angina pectoris and 36 (47 percent) had chest pain typical of anigina pectoris. In 18 of 19 patients the absence of chest pain correlated with the absence of coronary artery disease. The single patient without chest pain who had coronary artery disease had evidence of an inferior myocardial infarction in the electrocardiogram. Thus, absence of chest pain and the absence of electrocardiographic evidence of infarction predicted the absence of coronary disease in all cases. The presence of chest pain did not predict the presence of coronary artery disease, but the more typical the pain of angina pectoris the more likely were patients to have significant coronary artery disease. Of the 21 patients with atypical chest pain, 6 (29 percent) had coronary artery disease, but of the 36 patients with typical angina pectoris 23 (64 percent) had significant coronary artery disease. In addition, when patients with chest pain not typical of angina pectoris also had coronary artery disease, the diseased vessels usually supplied smaller areas of the left ventricle than when the pain was typical of angina pectoris. In 21 of 23 patients (91 percent) with typical angina pectoris and significant coronary artery disease, lesions were present in the left coronary artery. There was no systolic pressure gradient across the aortic valve that excluded the presence of coronary artery disease, although all patients with a calculated aortic valve area of less than 0.4 cm2 were free of coronary artery disease. Patients with severe left ventricular dysfunction were more likely to have normal coronary arteries.

Traumatic right coronary arterial-right atrial fistula.

A healthy 25 year old man presented with a machinery murmur and a history of a penetrating thoracic injury. Hemodynamic and angiographic evaluation demonstrated a fistula from the right coronary artery to the right atrium that was later successfully repaired. This case and similar reported cases indicate that fistula formation is a late complication of penetrating thoracic injuries. The onset of the murmur occurs with enlargement of the fistula and typically is delayed for several weeks to months after the initial injury.

Intravenous amiodarone for the rapid treatment of life-threatening ventricular arrhythmias in critically ill patients with coronary artery disease.

This study examined the effectiveness of intravenous amiodarone for rapid control and prevention of recurrent life-threatening ventricular tachyarrhythmias associated with cardiovascular collapse. In 22 critically ill patients with coronary artery disease (mean ejection fraction 27 +/- 13%), recurrent ventricular tachyarrhythmias proved refractory to 3.7 +/- 1.1 (mean +/- standard deviation) conventional antiarrhythmic drugs. In the 24-hour period before intravenous amiodarone treatment, patients experienced 2.4 +/- 2.3 (range 1 to 9) episodes of life-threatening ventricular tachycardia, ventricular fibrillation or both, requiring 4.0 +/- 3.9 direct current cardioversions. Within the 24 hours after initiation of intravenous amiodarone therapy (900 to 1,600 mg/day), 20 of 22 patients remained alive and had 1.1 +/- 1.6 episodes of life-threatening ventricular arrhythmias, requiring 1.9 +/- 3.1 direct current cardioversions. In the second 24-hour period, there were 19 survivors and life-threatening arrhythmias were reduced to 0.4 +/- 0.7 episode/patient requiring 0.4 +/- 0.9 direct current cardioversion. Overall, arrhythmias were controlled in 11 of 22 (50%) patients within the first 24 hours, and in 14 of 22 (64%) in the second 24 hours. Intravenous amiodarone therapy was well tolerated. Twelve patients were discharged from the hospital and 8 remained alive at a mean follow-up of 22 +/- 14 months. Thus, in critically ill patients, intravenous amiodarone may be useful for rapid control of spontaneous, refractory, life-threatening ventricular tachyarrhythmias.

Frequency of success and complications of coronary angioplasty of a stenosis at the ostium of a branch vessel.

The authors of this study hypothesized that percutaneous transluminal coronary angioplasty of a stenosis at the ostium of a branch vessel, whether isolated or associated with a bifurcation stenosis, was associated with reduced procedural success and increased in-hospital complications. One hundred six patients with 119 ostial branch stenoses were compared with 1,168 patients who underwent angioplasty of nonostial branch stenoses. An ostial branch stenosis was defined as a stenosis in the proximal 3 mm of a major branch vessel (diagonal [n = 58], posterior descending [n = 21], obtuse marginal [n = 34] and intermediate [n = 6]). The ostial branch stenosis was isolated in 61% of the patients and associated with a bifurcation stenosis in 39%. Despite a balloon to artery ratio of 1.05:1, angiographic success was 74% of ostial branch stenoses versus 91% of nonostial stenoses (p less than 0.01). Furthermore, angioplasty of ostial branch stenoses resulted in a complication rate of 13 versus 5% for angioplasty of nonostial branch stenoses (p less than 0.01). Therefore, angioplasty of ostial branch stenoses results in decreased procedural success and significant residual stenosis despite adequate balloon sizing, suggesting arterial elastic recoil and a significant increase in complications.

Lessons from the post coronary artery bypass graft study in evaluating and controlling technical variability in angiographic trials. Post CABG Investigators.

Although many investigators have evaluated the technical variability of quantitative angiographic techniques used to study atherosclerosis regression in native coronary arteries, few have studied the variability inherent in repeated studies of atherosclerotic saphenous vein grafts. This study describes 2 studies performed during the course of the Post Coronary Artery Bypass Graft (CABG) Clinical Trial that were designed to assess the reproducibility of: (1) repeated angiographic views within a short time period; and (2) reproducibility of the total process of quantitative analysis of saphenous vein graft angiograms. Statistical methods are described that provide a more meaningful assessment of the impact of measurement variability in the analytic process versus the variability related to changes induced by pharmacologic interventions. One such method, the increase in standard deviation (SD) among patients (ISDP), showed that repeated angiographic views increased the variability of calculation of lesion minimal diameter by 1.5%, whereas the ISDP for repetition of the entire process of quantitative angiographic readings increased variability 6.4%. These data from the Post CABG trial reveal that technical variability is small and has negligible impact on the conclusions of the study.

Cardiac amyloidosis in hereditary neuropathic amyloidosis diagnosed by endomyocardial biopsy.

A 57 year old male first developed progressive neuropathy of the lower extremities and then similar involvement in the upper extremities. Two years later he developed dyspnea and then complete atrioventricular block requiring the use of a permanent cardiac pacemaker. An older brother had an almost identical clinical course, including the installation of a permanent pacemaker. Both died of left ventricular failure. An endomyocardial biopsy revealed extensive amyloidosis and fibrosis of the myocardium. This is the first report of a myocardial biopsy showing amyloid on electron microscopy.

Effect of propranolol on respiratory function and exercise tolerance in patients with chronic obstructive lung disease.

Ten patients with chronic obstructive lung disease (COLD) (group 1) and five patients with combined COLD and cardiac disease (group 2) were studied at rest and during exercise after an intravenous (IV) slaine control followed by IV propranolol (0.2 mg/kg). During rest propranolol did not alter significantly measurements of lung volume in groups 1 or 2. Following propranolol the mean airway resistance (AR) in group 1 increased from 4.49 to 5.2 cm H2O/L/sec (P smaller than 0.02) and airway conductance (Gaw) decreased from 0.28 to 0.24 L/sec-1 cm. H2O1 (P smaller than 0.02). In group 2 following propranolol, the mean AR increased from 3.60 to 4.67 cm H2O1 (P smaller than 0.05), and Gaw decreased from 0.30 to 0.23 L/sec-1/cm H2O1 (P smaller than 0.05). During exercise, from control to propranolol, the heart rate (HR), blood pressure (BP), and heart rate blood pressure (HR x BP) decreased significantly for both groups 1 and 2 except for the systolic pressure in group 2. The duration of exercise and exercising PO2 were not significantly altered from control to propranolol in groups 1 and 2, indicating that the small but statistically significant changes in AR and Gaw did not interfere with symptom tolerated maximal exercise in these patients and were therefore not clinically important.

The significance and prognosis of chronic bifascicular block.

The clinical course of 303 patients with bifascicular block was reviewed. Initially, 62% of the total group had evidence of heart disease. The highest frequency of heart disease was in patients with left bundle-branch block and first-degree atrioventricular block (78% or 22/28), while the lowest was in those with right bundle-branch block and left axis deviation (56% or 55/98). During the subsequent clinical course the occurrence of cardiovascular morbidity was greatest in patients who had left bundle-branch block and heart disease (55% or 49/89). Complete heart block occurred in only 11 patients. The highest incidence of complete heart block occurred in right bundle-branch block and left axis deviation when associated with heart disease, but the annual rate was only 4%/yr. Mortality was highest in those with left bundle-branch block, first-degree atrioventricular block, and left axis deviation (43%/yr). A one-year mortality of 65% (11/17) was noted for patients who had bifascicular block prior to the time of acute myocardial infarction.

Aortic dissection presenting as pericarditis.

In five patients with aortic dissection, signs and/or symptoms of pericarditis were part of the early manifestations of the aortic disease. Signs of inflammatory pericarditis were noted clinically in four patients and were found at autopsy in one. In the three nonoperated patients who died of aortic rupture leading to fatal hemopericardium, symptoms of pericarditis preceded fatal rupture of the aorta by four to five days. A fourth patient died after surgical repair of aortic dissection 35 days after the onset of pericarditis. In the fifth patient, manifestations of chronic constrictive pericardial disease occurred over a period of seven months after which old aortic dissection was first identified. In each case, the internal tear of classic aortic dissection was located in the ascending aorta. Microscopic evidence of cystic medial necrosis of the aorta was present in each case. In each of two cases, there was a congenital bicuspid aortic valve. The phenomenon observed represents acute aortic dissection in which slow penetration of blood into the pericardial space caused inflammatory pericarditis. The interval between the onset of pericarditis and rupture of the aorta may allow sufficient time for appropriate diagnosis and potentially lifesaving treatment of the aortic disease.

Occlusion of Medtronic Hall mitral valve prosthesis by ruptured papillary muscle and chordae tendineae.

A 63-year-old woman had an unusual, but lethal complication after mitral valve replacement. Six hours after the operation, the ruptured head of the posterior papillary muscle migrated between the valve ring and disc and caused the disc to be wedged tightly shut. This complication appears to be unique to a tilting disc prosthesis.

Exercising pulmonary blood flow in mitral stenosis with anomalous pulmonary venous connection.

Exercising pulmonary blood flow was estimated from indicator-dilution curves in a patient with the infrequent combination of rheumatic mitral stenosis and anomalous pulmonary venous connection from the left lung. During supine exercise against progressively increasing external workloads, the proportion of flow to each lung remained nearly constant. The pulmonary vascular resistance was highest in the left lung, which emptied into the low-pressure systemic vein. Although right and left atrial pressures differed markedly during supine exercise, the proportion of pulmonary blood flow shunted to the systemic venous sytem remained essentially unchanged.