The Framingham Offspring Study: a commentary. 1980.

Forty-three of 1,312 men aged 35 to 54 years in the Framingham Offspring Study had clinically recognized coronary heart disease at the initial examination. Twenty-six men in this group had previously had a myocardial infarction. Of 1,296 women in the same age range, only 11 had coronary disease and 3 a prior myocardial infarction. The prevalence of coronary heart disease in men was strongly associated with age, smoking, high density lipoprotein (HDL), low density lipoprotein (LDL) and total cholesterol using univariate analyses. When multivariate logistic regression analysis was used, age, smoking and HDL and LDL cholesterol retained their significant association with coronary heart disease. The total cholesterol/HDL cholesterol ratio was also strongly associated with coronary heart disease in the multivariate analysis. It is concluded that both HDL and LDL cholesterol are strongly and independently associated with the prevalence of coronary heart disease, whereas the level of very low density lipoprotein cholesterol makes no statistically significant independent contribution.

Deciding when hemodynamic monitoring is appropriate. How will the data affect your diagnostic or therapeutic approach?

Hemodynamic data can be used to differentiate a variety of cardiopulmonary disorders, including right ventricular dysfunction, massive pulmonary embolism, and precapillary pulmonary hypertension. In patients with acute pulmonary edema, low-output states, or shock, hemodynamic measurements can help guide therapy; they also provide a precise estimate of a patient's response to vasoactive or inotropic drugs. Consider a flotation catheter for patients with complicated MIs, critically ill patients with multiorgan or major organ dysfunction, and high-risk cardiac patients undergoing surgery.

The pulmonary artery catheter.

First developed more than 20 years ago as a research tool for investigations of myocardial infarction, the pulmonary artery or Swan-Ganz catheter has gained general usage as a valuable clinical tool. Its development paralleled the rapid growth of technological advancements in clinical medicine. Rapid incorporation of technological advancements into clinical practice, however, is not without risk. Care must be taken to assure that clinicians possess the understanding of both basic concepts and requisite hardware to provide quality patient care. Equipment selection and calibration, patient selection, data interpretation, potential complications, troubleshooting, and procedure limitations must all be considered. Broader application of the Swan-Ganz catheter in surgery, anesthesiology, and critical care as well as in cardiology has provided information on hemodynamics that has had considerable impact on diagnostics as well as on therapy for patients with a wide variety of clinical conditions.

Prospective evaluation of ultrafast cardiac computed tomography for determination of coronary bypass graft patency.

Twenty-five consecutive patients with 68 independent (single distal anastomosis) saphenous vein aortocoronary and 12 internal mammary bypass grafts (27 to left anterior descending, 10 to diagonal, 23 to left circumflex, 20 to right coronary artery) entered a reader-blinded, prospective, standardized study to establish the accuracy of ultrafast (cine) cardiac computed tomography (CT) for determining graft patency compared with invasive angiography. All patients underwent imaging after injection of 35 to 45 ml of meglumine diatrizoate (Renografin-76; 7 to 9 ml/sec for 5 sec) into an arm vein. Electrocardiographically triggered images were acquired over eight to 16 tomographic levels at 1 cm intervals from aortic arch to mid left ventricle. Criteria for graft patency were contrast opacification on at least two noncontinguous levels and contrast density-time curves morphologically similar to that of the aorta. Ultrafast CT correctly determined that 46 of 48 bypass grafts were patent and 31 of 32 were occluded (sensitivity, specificity, and accuracy 96%, 97%, and 96%); there were no interpretation errors in 23 (92%) of the 25 patients. Accuracy was independent of vessel bypassed and not different for saphenous veins (96%) compared with internal mammary bypasses (100%). This study establishes a 20 min outpatient intravenous injection technique that is highly accurate for determining patency of coronary artery bypass grafts.

Prediction of death, myocardial infarction, and worsening chest pain using thallium scintigraphy and exercise electrocardiography.

Although used extensively, there is little published information on the prognostic ability of exercise 201Tl scintigraphy. Accordingly, 1 yr after testing we contacted 819 patients without previous MI or CABG seen in our laboratory during a 2-yr period. Events were defined as death from a cardiovascular cause, nonfatal MI, or worsening clinical state requiring CABG. The event rate was 3.9 events per 100 patients per year. There was univariate prognostic information when comparing the highest and lowest categories as risk ratios for chest pain characteristics (2.7), sex (2.3), exercise duration (3.1), ST slope (2.5), and thallium pattern (11.6), intensity of perfusion defect (17.2), and number of abnormal regions (8.7). However, the strongest predictors were also the least common. Prognostic ability was improved by combining the results categorically, as the number of abnormal tests (13.9). The highest risk ratio, 20.5:1, was obtained by combining results through discriminant function analysis. We conclude that exercise thallium scintigraphy provides prognostic information, although the most predictive patterns are uncommon. Combining the results of multiple test results improves the prognostic ability.

Effects of hematoporphyrin derivative and photodynamic therapy on atherosclerotic rabbits.

This study was performed to demonstrate selective uptake of hematoporphyrin derivative (HPD) within actively developing atheroma, to localize the site of uptake of HPD within the atheroma, and to determine the potential for photodynamic therapy (PDT) of atherosclerosis in the rabbit model. Fifteen rabbits were rendered atherosclerotic. Five rabbits received neither HPD nor PDT and 2 rabbits received HPD, 10 mg/kg intravenously, without subsequent irradiation. Eight other rabbits received 5 to 20 mg of HPD intravenously and subsequent intravascular 636-nm laser radiation to either the thoracic aorta or the aortic arch. A total of 32 to 288 J of laser energy was delivered through a 300-mu quartz fiber. All rabbits that received in vivo HPD had red fluorescence of their aortas when placed under ultraviolet light. The pattern of fluorescence corresponded precisely to the pattern of atheroma. In segments that received PDT, light microscopic examination revealed an accumulation of smooth muscle cells at the intimal surface. Fluorescence microscopy revealed a diminishing concentration gradient of HPD from intimal surface layers towards the media. Assessment of treated thoracic aortic segments revealed quantitative and qualitative differences compared with control segments. In the arch-treated segments, however, no changes were seen. It is concluded that HPD localizes within rabbit atheroma, can be detected by fluorescence and is deposited in a diminishing concentration gradient from lumen toward media. Irradiation with 636-nm light may induce qualitative and quantitative changes in atheroma.

Delineation of peripheral and coronary detail by intraoperative angioscopy.

In this study, the development of intraoperative angioscopy, the value of the information obtained, and the problems encountered with the procedure are reported. Eight angioscopes, 1.5 to 2.8 mm in diameter, with a line resolution of greater than 0.4 mm at 5 mm, were used. One-hundred ten angioscopic investigations were performed in 46 patients; 24 at peripheral bypass surgery and 22 at coronary artery bypass surgery. These included 68 arteries, 28 new anastomoses, six old grafts, five laser angioplasties, and three in situ vein grafts. The most important finding was that angioscopic data provide information not available from probes or angiography. Angioscopic findings were responsible for a change in surgical procedures in 12 patients (26%) including three anastomotic revisions, three alterations in graft site placement, and two repeat thrombectomies. The most significant technical problems were lack of steerability and insufficient irrigation, which resulted in poor angiographic images. Further technical development is necessary before routine intraoperative angioscopy is practical. Nevertheless, if these problems are resolved, angioscopy will provide unique, high-resolution information which can directly alter surgical therapy.

Laser ablation of human atherosclerotic plaque without adjacent tissue injury.

Seventy samples of human cadaver atherosclerotic aorta were irradiated in vitro using a 308 nm xenon chloride excimer laser. Energy per pulse, pulse duration and frequency were varied. For comparison, 60 segments were also irradiated with an argon ion and an Nd:YAG (neodymium:yttrium aluminum garnet) laser operated in the continuous mode. Tissue was fixed in formalin, sectioned and examined microscopically. The Nd:YAG and argon ion-irradiated tissue exhibited a central crater with irregular edges and concentric zones of thermal and blast injury. In contrast, the excimer laser-irradiated tissue had narrow deep incisions with minimal or no thermal injury. These preliminary experiments indicate that the excimer laser vaporizes tissue in a manner different from that of the continuous wave Nd:YAG or argon ion laser. The sharp incision margins and minimal damage to adjacent normal tissue suggest that the excimer laser is more desirable for general surgical and intravascular uses than are the conventionally used medical lasers.

Nonsurgical reperfusion in evolving myocardial infarction.

Nonsurgical recanalization of the occluded coronary artery has been performed in patients with evolving myocardial infarction since the late 1970s by intracoronary administration of thrombolytic agents at the ostium of the occluded artery or directly to the site of occlusion. The authors review the basic concepts underlying intracoronary thrombolysis, the method applied at their institution and the clinical results. Reperfusion of totally occluded arteries or termination of the ischemic state in subtotally occluded arteries was achieved in 71 (87.7%) of 81 patients. Reocclusion occurred in four patients, in three of these at a time when anticoagulation became temporarily ineffective, emphasizing the need for uninterrupted anticoagulation with a partial thromboplastin time longer than 80 seconds. Thallium scintigraphic studies before and after reperfusion showed a decrease in defect, indicating myocardial salvage, in the successful cases but not in failures or untreated control subjects. A decrease in thallium-201 defect was followed by improvement of regional wall motion and usually also left ventricular ejection fraction. Three of the patients with an unsuccessful result and one patient with a successful result died. Bypass surgery was performed electively in 18 patients because of multiple vessel involvement. Intracoronary thrombolysis appears to be a relatively safe and promising procedure. A large controlled study will be needed for definitive assessment of its role in the management of acute myocardial infarction.

Hemodynamic measurements in clinical practice: a decade in review.

Hemodynamic measurement is now an important and feasible adjunct to clinical practice. Its successful application to alleviate illness in human beings is evident in its contribution to an understanding of the pathophysiology of disease and the efficacy of various interventions to alter the course of a variety of diseases. Its application is widespread in the high risk patient undergoing surgery and the critically ill medically treated patient. Hemodynamic measurement permits accurate determination of the state and, if necessary, of the continuously changing function of the heart as related to disease process and guides treatment and interventions on a rational physiologic basis.

Preoperative prediction of reversible myocardial asynergy by postexercise radionuclide ventriculography.

Myocardial asynergy is sometimes reversed by coronary bypass, and a noninvasive method of predicting which assess are reversible would be desirable. To assess whether changes in myocardial wall motion observed immediately after exercise can differentiate reversible from nonreversible myocardial asynergy, we evaluated 53 patients by radionuclide ventriculography before and after exercise and again at rest after coronary bypass surgery. Preoperative improvement in wall motion immediately after exercise was highly predictive of the surgical outcome (average chance-corrected agreement, 91 per cent). At surgery the asynergic segments that had improved after exercise were free of grossly apparent epicardial scarring. The accuracy of these predictions for postoperative improvement was significantly greater (P less than 0.01) than that of analysis of Q waves on resting electrocardiography (average chance-corrected agreement, 40 per cent). In contrast, preoperative changes in left ventricular ejection fraction after exercise were not predictive of postoperative resting ejection fraction. We conclude that postexercise radionuclide ventriculography can be used to identify reversible resting myocardial asynergy. This test should prove effective in predicting which patients with myocardial asynergy are most likely to benefit from aortocoronary revascularization.

Intracoronary thrombolysis in acute myocardial infarction: experimental background and clinical experience.

Occlusive intracoronary (IC) thrombosis was produced experimentally in dogs by placement of a copper coil. The thrombus was consistently lysed by application of Thrombolysin (streptokinase and plasminogen) at the site of occlusion, 1 to 6 hours after thrombosis. Thrombolysin has no toxic effect on the coronary artery wall or the myocardium. Reperfusion after 30 to 60 minutes of occlusion frequently resulted in ventricular fibrillation, but gradual reperfusion reduced the probability of ventricular fibrillation. Intramyocardial bleeding was noted after reperfusion in areas of advanced necrosis and was shown to be the consequence, rather than the cause, of necrosis. The reperfused myocardium remained hypocontractile, but in contrast to the occlusion period, its mechanical function could be enhanced by inotropic stimulation. After experimental studies confirmed the feasibility and safety of IC thrombolysis, the technique was applied within 3 hours of onset of pain in 29 patients with evolving acute myocardial infarction (AMI) and showing ST elevations without pathologic Q waves. Nitroglycerin (NTG), 0.1 mg, was injected into the occluded coronary artery to rule out spasm; NTG failed to open the occluded artery. A special, very flexible, radiopaque No. 2 French catheter was advanced through the angiography catheter to the site of occlusion. Thrombolysin was infused at a rate of 4000 to 6000 IU/min until patency was achieved, followed by 2000 IU/min for 60 minutes. Lysis of clot was achieved in 27 of 29 patients. The single death (unrelated to the procedure) occurred subsequently in a patient in whom the artery was not reopened. After successful thrombolysis, 12 patients underwent elective coronary bypass surgery because of multiple stenoses. The need for early reperfusion is emphasized for effective IC thrombolysis therapy in evolving AMI.

Use of thallium-201 redistribution scintigraphy in the preoperative differentiation of reversible and nonreversible myocardial asynergy.

Thallium-201 (201Tl) redistribution scintigraphy might differentiate reversibly from nonreversibly asynergic myocardial segments and thus predict the response of these segments to coronary artery bypass grafting (CABG). To test this hypothesis, 25 consecutive patients undergoing CABG, preoperative stress-redistribution 201Tl scintigraphy, and both pre- and postoperative resting equilibrium radionuclide ventriculography were evaluated. For both types of scintigraphic study, each patient was imaged in the same three views. Because of the effects of CABG on septal motion, this region was considered separately. Postoperative improvement was noted in 54% of 72 preoperative asynergic segments. Improvement was common not only in hypokinetic but also in akinetic and dyskinetic segments, and occurred in a similar proportion of studies performed early (less than 2 weeks) or late (3-6 months) after CABG. Thallium-201 redistribution scintigraphy was highly predictive of the pattern of postoperative asynergy: The redistribution pattern was normal in 90% of segments with reversible asynergy and abnormal in 76% of segments with nonreversible asynergy. The presence or absence of pathologic Q waves was less sensitive in this differentiation. Septal segments, however, frequently demonstrated abnormal wall motion postoperatively, despite normal 201Tl redistribution scintigraphy. Resting left ventricular ejection fraction (LVEF) was generally unchanged postoperatively, but in some patients with multiple areas of reversible asynergy it did improve. Thus, 201Tl redistribution scintigraphy appears to reliably distinguish viable from nonviable asynergic myocardial zones, and predicts the response of these segments to CABG.

Thallium myocardial scintigraphy and its use in the assessment of coronary artery disease.

Since coronary artery disease often first manifests as sudden death or myocardial infarction before symptoms develop, the early detection of disease may identify patients at risk for an acute event. Stress redistribution thallium-201 scintigraphy provides a useful, noninvasive method for assessing the presence of CAD as well as for evaluating the extent of disease. The principles and methods of thallium scintigraphy are described herein in addition to its clinical application. The availability of noninvasive thallium-201 scintigraphy has added to the physician's ability to accurately diagnose CAD, to objectively evaluate the effects of coronary artery bypass surgery, and to assess patients with acute myocardial infarction.

Quantification of myocardial injury during coronary artery bypass graft.

Serial intraoperative myocardial-specific creatine-kinase (MB-CK) samples were obtained in 32 patients undergoing coronary artery bypass graft (CABG). Based upon their postoperative ECG and technetium pyrophosphate SCAN results, each patient was classified as either Group A (MI), B (normal), or C (equivocal). Peak MB-CK was reported for each group. The mean value for Group A (75 +/- 17 IU/L) is higher than for Group B (18 +/- 1 IU/L) or Group C (30 +/- IU/L). The concept of measuring and a formula for calculation of intraoperative myocardial injury are presented. The mean value for Group A (MI, 10,709 +/- 5885) is higher than either groups B (normal) or C (equivocal) by a test of proportionality (P < 0.001). Likewise, Group C (898 +/- 159) is higher than B (466 +/- 71) (P < 0.05). This index, while in need of further validation, corresponds closely to the clinical status of the 32 patients studied and should provide a means more refined than mortality or incidence of MI upon which to judge efficacy of any proposed means of operative myocardial preservation.

Coronary sinus blood flow and sampling for detection of unrecognized myocardial ischemia and injury.

Fifteen patients were studied to detect unrecognized intraoperative ischemia or necrosis in perioperative myocardial infarction (MI) associated with coronary bypass. Simultaneous arterial and coronary sinus blood samples were analyzed for lactate and both total and MB-CPK. Coronary sinus flow measurements were done coincident with sampling in seven patients. Five had perioperative MI diagnosed by positive pyrophosphate scan and electrocardiogram. Although normal initially (mean 19 +/- 5.0%), lactate extraction after thoracotomy, before aortic cross-clamping, became abnormal in 12 patients with more pronounced abnormality in those with perioperative MI (-19 +/- 9.0%). Net efflux of lactate was higher in perioperative MI (mean 0.6 +/- 0.2 vs 0.016 +/- 0.04 mM/L) than in non-MI patients. All patients had detectable total and MB-CPK (mean 295 and 31 IU/L, respectively) and all those with coronary disease had a positive arterial-coronary sinus gradient for MB-CPK (mean 9 IU/L). Perioperative MI patients had a higher gradient than non-MI patients (mean 25 vs 2 IU/L) and with one exception that gradient exceeded 5-7 IU/L. It is concluded that severe ischemia before aortic cross-clamping precedes perioperative MI and may contribute to release of CPK into coronary sinus blood. Improvement in the techniques of anesthesia and intraoperative myocardial preservation are suggested.