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.

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.

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.

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.

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.

Safety of coronary arteriography in clinically stable patients following coronary bypass surgery. Post CABG Clinical Trial Investigators.

The frequent use of diagnostic coronary arteriography and its importance in evaluating results of intervention in clinical trials emphasize the necessity of continued assessment of procedural risk. Several studies have described such risks, but they have often included a diverse group of patients with varying levels of clinical stability. Furthermore, this risk has not been well established in a population of patients with saphenous vein bypass grafts. There is need to define the risk of coronary arteriography in a group of patients who are both clinically similar and stable, and to evaluate the influence of improved technology and increased operator experience on the risk of the procedure. The National Heart, Lung, and Blood Institute-funded Post Coronary Artery Bypass Graft Trial offered the opportunity to evaluate the risk of elective diagnostic coronary arteriography in clinically stable patients studied at two points in time: pre-enrollment and 4-5 years after study entry. In this group of 2,635 angiograms from clinically stable patients over 5 years there were no deaths and the risk of myocardial infarction was 0.08%, while 0.7% had clinically important complications. Non-elective, urgent studies (311 angiograms) on unstable patients were more likely to include angioplasty and were associated with a risk of death of 0.6% and myocardial infarction of 1.3%. Complications did not vary with age or gender. Vascular trauma was more likely to occur using the brachial than the femoral artery entry sites. These results indicate that elective angiography on stable patients can be accomplished with a very low risk of mortality (0% in this study) or serious cardiovascular complication. This supports the safety and usefulness of angiography for clinical intervention trials.

Transesophageal echocardiography in patients with mechanical circulatory assistance.

Transesophageal echocardiography was used to assess myocardial function and to detect complications after mechanical circulatory support for 8 patients with cardiogenic shock. In 3 of 8 patients, serial transesophageal echocardiography documented improvement of systolic ventricular function, and it was possible to wean these 3 patients from the ventricular assist device. In all patients, transesophageal echocardiography added clinically important information including the extent of left and right ventricular dysfunction (6 patients), presence of atrial or ventricular thrombus (5 patients), presence of pericardial effusion or clot (2 patients), and verification of the position of the intravascular device (1 patient). Thus, transesophageal echocardiography may provide clinically useful information regarding both the underlying cardiac disease and potential complications from the mechanical circulatory assistance.

The Ultra-Select guidewire: a new nitinol guidewire for coronary angioplasty.

The Ultra Select¿ guidewire is a solid nitinol core torque wire that recently became available for use in coronary angioplasty. This wire has near one-to-one torque with kink resistant axial strength. The wire is radioopaque and highly visible. It is effective in negotiating severe tortuosity. Nitinol (nickel-titanium alloy) has unique properties that allow for specific performance advantages for use in coronary angioplasty. This report discusses this new guidewire and its use in coronary angioplasty.

Coronary angioplasty in stenotic lesions adjacent to coronary aneurysms.

The efficacy and safety of coronary angioplasty for stenoses adjacent to coronary aneurysms were studied in 25 patients (19 men and 6 women, mean age 62 +/- 11 years). The study represented 1.1% of patients undergoing coronary angioplasty during the study time period. The aneurysm diameter exceeded 1.8 +/- 0.2 times the normal artery diameter. Eleven (44%) of these aneurysms were localized in the left anterior descending, 3 (12%) in the circumflex and 11 (44%) in the right coronary artery. Percent diameter stenosis was reduced from 72 +/- 10% to 23 +/- 19%, and transstenotic gradient from 51 +/- 13 to 15 +/- 9 mmHg when measured. Clinical success (absence of pain on discharge without coronary bypass surgery, death, or infarction) was achieved in 24 (96%) patients. In one patient acute vessel closure occurred. No embolic events or coronary artery rupture occurred. Seventeen (71%) of the 24 successful patients remained asymptomatic at clinical follow-up (mean = 7.7 +/- 5.0 months). At late follow-up, one patient had sustained a myocardial infarction, two had elective bypass surgery, and two had successful repeat angioplasty. The data from this small patient population suggest that angioplasty for a stenosis adjacent to a coronary aneurysm can be performed safely with a high primary success rate.

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.

Clinical application of percutaneous cardiopulmonary bypass for high risk coronary angioplasty.

Percutaneous cardiopulmonary bypass support was electively instituted prior to coronary angioplasty in 16 patients at high risk for hemodynamic collapse. In all cases the dilated artery supplied greater than 2/3 of the functioning myocardium. Eight patients had moderate LV dysfunction with ejection fraction 25-40%. Eight patients had an ejection fraction less than 20%. A 21 French cannula and a 17 French cannula were percutaneously inserted into the femoral vein and artery. Cardiopulmonary bypass support was instituted using a Bio-Medicus centrifugal pump just prior to coronary angioplasty at flow rates of 3.5-5 liters/minute. Thirteen patients had single vessel angioplasty and three patients had multivessel angioplasty. Complete loss of systolic function was observed in 9 (56%) patients. This finding when present confirms the absolute requirement for cardiopulmonary support. Technical success was achieved in all 16 patients (100%), clinical success was achieved in 14 patients (88%). Patient followup (mean 10 months) revealed 3 patients with class I-II angina and 10 patients were asymptomatic. There was one late death. In conclusion, percutaneous cardiopulmonary bypass support for carefully selected high risk patients may allow coronary angioplasty to be performed safely and effectively despite complete loss of systolic function during balloon inflation.

Thermodilution cardiac output values obtained by using a centrally placed introducer sheath and right atrial port of a pulmonary artery catheter.

Thermodilution cardiac output measurements obtained using a centrally placed introducer sheath were compared with thermodilution cardiac outputs obtained using the right atrial port of a balloon-tip, flow-directed pulmonary artery catheter in 15 patients with cardiac failure. Cardiac output values were obtained by manually injecting 10 ml of iced, D5W alternately through the introducer sheath and the right atrial port of the flow-directed catheter. Thirty cardiac output readings were obtained in the 15 patients. Cardiac outputs obtained using the right atrial port (CORA) did not differ significantly from cardiac outputs obtained using the introducer sheath (COSP) (5.3 +/- 0.2 vs. 5.2 +/- 0.2 L/min). The correlation between CORA and COSP was significant (r = .94, p less than .0001) and could be described by the formula CORA = 0.33 + 0.96 COSP. We conclude that when the right atrial port of a flow-directed catheter is nonfunctional, a thermodilution cardiac output obtained using a centrally placed introducer sheath offers a reliable alternative.

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.

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.

Histologic evidence of angiographic catheter-induced vascular trauma: a comparison of conventional and deformable soft-tip catheters.

Catheter-related complications associated with coronary arteriography remain an iatrogenic hazard with life-threatening consequences. Because such complications may be related to catheter-tip-induced vascular trauma during coronary angiography or percutaneous transluminal coronary angioplasty (PTCA), several types of deformable, soft-tip angiographic catheters have been developed. The following study was undertaken to evaluate the effects of one of these catheters, as well as of conventional catheters, in canine arteries. Ten dogs were catheterized, five with a conventional angiographic catheter and five with a deformable soft-tip catheter (Angiomedics SOFTIP model), all in the Judkins left 3.5 configuration. The left coronary artery (LCA) was subjected to repeated catheterization; the instruments were also advanced and withdrawn through various segments of the thoracic and abdominal aorta and the right iliac artery. Forty-five arterial tissue sections were collected; these were subjected to histologic analysis 2 weeks after catheterization. When catheterized with the soft-tip instrument, muscular arteries such as the LCA and the right iliac artery had an 86% reduction in subintimal lesions with a disrupted or split internal elastic membrane, compared to muscular arteries catheterized with a conventional instrument (p <.017). Moreover, two medial tears were produced by the conventional catheters. On a scale of 1 to 3 (3 being the most severe), the average severity of muscular arterial lesions observed after use of the soft-tip catheter was 1.0, whereas the average severity associated with conventional catheters was 2.0 (p <.02). No significant differences were observed in elastic (aortic) segments. Therefore, this study showed that subacute, subintimal vascular lesions induced by conventional angiographic catheters are more frequent, more serious, and more likely to penetrate the internal elastic membrane than are lesions produced by soft-tip catheters. Obviously, then, soft-tip catheters offer a safer, less traumatic approach to diagnostic and interventional cardiology.

[Comparison of 3 ECG computer programs with interpretation by physicians]. / Vergleich von 3 EKG-Computer-Programmen mit der Interpretation durch Arzte.

Three ECG computer programs-Hewlett Packard analog program (HP), Telemed analog program (T) and Marquette 12 SL digital program (MAC)-were evaluated and their accuracy of ECG reading compared with the reading of 4 experienced interpreters on 140 ECGs of patients with various clinical abnormalities. Major disagreement with effect on patient management, and minor disagreement were defined at a joint session with a senior (consensus). The computers identified all normal ECGs correctly (sensitivity 100%). The percentage of major agreements (full agreements and minor disagreements) between consensus and computer was 79% for HP, 90% for T and 93% for MAC. The number of disagreements varied widely between readers and in relation to the different computers. Major problems for the computers were the interpretation of rhythm disturbances and the diagnosis of myocardial infarction, T-wave changes and ventricular hypertrophy: major diagnoses missed by the readers were first degree AV block, QT prolongation, and myocardial infarction. Although there was a considerable difference of accuracy between the 3 computer systems, all of them are sufficiently accurate to be useful to most clinicians. However, every ECG should be over-read by a physician, particularly if a clinical decision is based on the ECG diagnosis.

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.