Lloyd W. Klein

Prognostic significance of severe narrowing of the proximal portion of the left anterior descending coronary artery

To determine the prognostic importance of significant narrowings involving the proximal left anterior descending coronary artery (LAD), 866 medically treated patients with significant coronary artery disease (CAD) were followed after cardiac catheterization for a mean of 17 months (range 1 to 46). Coronary narrowings in all patients were evaluated based on site relative to large branches and on angiographic severity. Prognosis was best predicted by the presence of at least 70% diameter reductions in the LAD before the first 2 large branches (chi 2 = 16, p = 0.0001). At 3 years, there was a 94% cumulative survival rate in patients with less than 70% stenoses at this location, but an 82% survival rate in patients with 70% or more stenoses (p less than 0.0001). In addition, although the presence of proximal LAD narrowings was the best predictor of prognosis in patients with a low global ejection fraction, this was not so in patients with normal ejection fractions, as this subgroup had an excellent overall prognosis. Thus, the presence and severity of significant stenoses in the proximal LAD are stronger predictors of prognosis than stenoses elsewhere in the major coronary arteries. The presence of an angiographically significant narrowing in this anatomic location is highly correlated with an increased 1- to 3-year mortality rate.

Prognosis of symptomatic coronary artery disease in young adults aged 40 years or less

The clinical course and coronary angiographic features of symptomatic coronary artery disease (CAD) in patients younger than 40 years old are described with particular emphasis on the prevalence of myocardial infarction and the degree of diminished functional capacity. Eighty-five patients with CAD proven by coronary angiography were studied. There were 73 men and 12 women aged 27 to 40 years. Fifty-nine patients presented with acute myocardial infarction, most of whom denied previous chest pain, and 14% (12 patients) presented with less acute chest pain syndromes. Coronary angiography was performed in all patients, and greater than or equal to 70% luminal diameter narrowing was considered significant. Coronary angiographic findings reveal 51% with 1-vessel CAD, 31% with 2-vessel and 19% with 3-vessel. Subsequently, 23 patients had coronary artery bypass graft surgery, 7 underwent angioplasty and 55 were treated medically. Follow-up for a mean of 3 years revealed only 1 death and 4 subsequent hospital admissions for cardiac events. Fifty-three percent of the patients are entirely pain free, and only 4 (5%) have significant symptoms of angina pectoris. Although 15 (18%) are not employed regularly, the remainder work full- or part-time, or plan to work in the near future. These data suggest that the short-term prognosis and functional status of young patients with CAD is excellent.

Rate of left ventricular functional recovery by radionuclide angiography after exercise in coronary artery disease

To characterize determinants of the rate of recovery of left ventricular (LV) function after exercise-induced ischemia, sequential postexercise radionuclide angiography was performed prospectively in 38 consecutive patients with documented coronary artery disease (CAD). In each patient new or increased regional asynergy developed or absolute ejection fraction decreased at least 4% during exercise. Twenty patients showed immediate recovery of LV function after exercise (group 1) and 18 showed delayed recovery (group 2). Ejection fraction in the first postexercise period was significantly greater in group 1 (65 +/- 12%) than in group 2 (55 +/- 11%) (p less than 0.01). The mean number of coronary arteries with at least 70% diameter narrowing was greater in group 2 (2.7 +/- 0.5) than in group 1 (2.0 +/- 0.9) (p = 0.026); CAD score was also greater in group 2 than in group 1 (p = 0.005). The increase in LV end-diastolic volume from rest to end exercise was greater in group 2 than in group 1 (p = 0.005); neither the change in LV volume nor the change in heart rate or blood pressure after exercise separated the groups. The only independent predictor of the rate of functional recovery was the degree of exercise-induced regional myocardial asynergy (p less than 0.001). Thus, exercise radionuclide angiography in patients with CAD provides a model for evaluating postischemic myocardial function. Delayed functional recovery is associated with extensive exercise-induced regional asynergy as a result of severe CAD and is not primarily influenced by hemodynamic changes.

Importance of total life consumption of cigarettes as a risk factor for coronary artery disease

Cigarette smoking is an established risk factor for the occurrence of cardiovascular events and mortality. Whether recent smoking history or total life consumption best represents the increased risk due to smoking has not been previously established. Thus, stepwise logistic regression analysis was used to determine the relative contributions of these factors to the risk of having significant coronary artery disease in 1,349 patients who underwent cardiac catheterization. Six risk factors were analyzed: total pack-years, current packs smoked per day, age, gender, family history and symptomatic status. The results of this analysis showed that total pack-years, but not current packs per day, is a significant independent risk factor for the development of coronary artery disease. This was true in every age group up to but not older than age 70 years. Although the overall risk was lower in younger patients and in patients with less typical symptoms of angina, the relative risk in cigarette smokers relative to pack-years was consistently greater. The risk of total life consumption of cigarettes is thus greater than has heretofore been realized, particularly in persons who would otherwise be categorized as low risk.

The Q-wave and non-Q wave myocardial infarction: differences and similarities.

I T IS STANDARD medical practice to divide myocardial infarctions into two types: the “transmural” infarction and the “nontransmural” or “subendocardial” infarction. Clinically, this distinction is made on the basis of the occurrence of new Q waves on the ECG. Customarily, if only ST segment or T wave changes occur without the development of Q waves, the infarction is classified as subendocardial, whereas those infarcts accompanied by new Q waves are considered to be transmural. Recently, however, there has been a major reevaluation of the differentiation between transmural and subendocardial myocardial infarctions.‘-3 The prognosis of patients sustaining subendocardial infarcts has traditionally been regarded as better than patients with transmural infarcts”; however, several recent studies have not supported this view.8-‘2 Even the value of the ECG criteria has been questioned because of the lack of specificity of the Q wave in identifying the transmural extent of infarction.‘3,‘4 The traditional view has been based primarily on the concept that since a smaller amount of myocardium is involved in a subendocardial infarct, the overall effect on left ventricular function is less. In addition, the in-hospital mortality for subendocardial infarcts was thought to be less. However, it is now increasingly clear that the outer myocardial layers remain in jeopardy after a subendocardial infarction, exposing the patient to the risk of a subsequent event following hospital discharge. Similarly, the validity of the Q wave to estimate the transmural depth of infarction, and by inference, to predict the likely shortand long-term course of such patients has been reevaluated as well. Is there enough evidence to support the continued use of the terms subendocardial and transmural and what are the consequences for patient management?

Quantification of absolute luminal diameter by computer-analyzed digital subtraction angiography: an assessment in human coronary arteries.

Determination of absolute lumen diameters has been shown to be useful in predicting the functional importance of a coronary stenosis. In this study, both single-plane and orthogonal biplane digital subtraction angiograms were obtained in human cadaver coronary arteries. A single absolute diameter was calculated at the site of greatest narrowing in 20 segments by two automated computerized algorithms. Minimum and maximum diameters at the site of the stenosis were measured from pathologic sections prepared after pressure fixation. Method 1, which determines the edges by means of the first derivative of the videodensity curve, derived absolute diameters that fell between the pathologic minimum and maximum in 10 of 20 segments. Method 2, which determines the edges by an average of the first and second derivatives of the videodensity change, derived absolute diameters that fell between the pathologic minimum and maximum diameters in 15 of 20 segments. Method 1 correlated well with the maximum pathologic diameter (r = .76) and less well with the minrmum pathologic diameter (r = .67). Method 2 correlated very well with the maximum pathologic diameter (r = .79) and also correlated well with the minimum pathologic diameter (r = .74). As would be expected, the computerized algorithms tended to overestimate the minimum pathologic diameter and to underestimate the maximum pathologic diameter. In six segments, two orthogonal views were analyzed; no further accuracy was discernible over single-plane determinations. Thus quantitative coronary angiography by digital subtraction angiography is sufficiently accurate to be of use in the measurement of the severity of a coronary stenosis.

Assessment of coronary artery stenoses by digital subtraction angiography: A pathoanatomic validation

Automated computer assessment of coronary stenoses from digital subtraction angiographic images comparing geometric and videodensitometric algorithms was performed. Digital subtraction angiograms were acquired on a 512 X 512 X 8 bit pixel matrix at 8 frames/second. Fifteen segments from nine human cadaver coronary arteries, with lesions ranging from 0% to 97%, were analyzed. Hand injections of radiopaque dye were made during the pulsatile infusion of saline solution at physiologic pressures and flows. Individual frames best demonstrating a lesion were digitally magnified and the stenosis was measured; the operator identified only the segment of interest. The artery was then injected with a rapidly hardening gel during the same rate of infusion as that used during image acquisition. Histologic sections were cut at 2 mm intervals after fixation and elastic stains applied. Photographs of the section comparable to the site determined from the angiogram were taken, and hand planimetry by a blinded investigator was performed. There was an excellent correlation between histopathology and videodensitometry (r = 0.93; p less than 0.0001). The two geometric algorithms studied also had very good correlations (r = 0.90 and 0.84) with pathology. Two experienced angiographers, despite excellent agreement with each other, had lower correlations with pathology than any of the three computer algorithms studied (r = 0.79 and 0.83, respectively), although this difference did not attain statistical significance. This in vitro model simulating in vivo conditions validates the use of automated videodensitometric and geometric computer algorithms to interpret coronary angiography and assess severity of stenosis.

Videodensitometric quantitation of aortic regurgitation by digital subtraction aortography using a computer-based method analyzing time-density curves

To assess the clinical role of computer analysis of time-density curves in the evaluation of aortic regurgitation (AR), digital subtraction aortography (DSA) and cineaortography were performed sequentially in 17 patients with varying degrees of AR (1+ to 4+) and in 4 control patients. DSA was performed at a rate of 30 frames/s on a 512 X 512 X 8 bit pixel matrix using the same total volume and injection rate, but with half the amount of contrast agent as standard cineaortography. A 30 X 30 pixel area of interest was identified in the aorta above the valve plane and in the left ventricle where the AR stream was seen. The density of both areas of interest and the ratio of left ventricular/aortic area of interest density was calculated in each frame and then plotted vs time. The ratio at the end of injection (LVd/Aod) had an excellent correlation with cineaortography (chi 2 = 19, p less than 0.001), ranging from 0 to 0.2 in patients with no AR, 0.2 to 0.5 in those with 1+ AR, 0.5 to 0.7 in those with 2+ AR, 0.7 to 0.9 in those with 3+ AR and more than 0.9 in those with 4+ AR. Thus, quantitative assessment of AR by computer analysis of time-density curves derived from DSA is a new and objective technique with significant clinical potential.

Medical and surgical survival in Coronary artery disease in the 1980s

The survival of 1,657 patients with angiographically proved coronary artery disease (CAD) was studied for 4 years (mean 2.0 +/- 1.2) during the 1980s to examine the prognostic importance of multiple clinical variables. One hundred of the 1,049 medically treated patients (9.5%) and 31 of the 608 surgically treated patients (5.1%) died. Multivariate analyses revealed that the strongest prognostic variables for survival in the medical group were indexes of left ventricular function (p less than 0.0001), severity of coronary stenoses (p less than 0.0001) and age (p = 0.005). However, only age (p less than 0.0001) was a significant prognostic variable in the surgically treated group. This study emphasizes the lack of prognostic significance of left ventricular function indexes and severity of coronary stenoses in surgically treated patients with CAD. These results continue the trend toward improved surgical survival shown in recent years.

The resolution of coronary collaterals after successful percutaneous transluminal coronary angioplasty

It has been shown that collaterals can develop rapidly during acute coronary occlusion, either due to thrombosis or during angioplasty (PTCA). However, the fate of well-developed collaterals immediately after a successful PTCA is unknown. Accordingly, 15 patients with Rentrop class 2 or 3 collaterals as visualized angiographically were studied immediately after successful single-vessel PTCA. The left anterior descending artery contained the stenosis in nine patients and the right coronary contained the stenosis in six patients. There was total occlusion of six vessels and subtotal occlusions of nine vessels pre PTCA. Immediately after PTCA, flow through the collaterals to the stenosed artery could no longer be visualized angiographically in eight patients (group 1), but remained faintly visible in seven patients (group 2). There was no difference between these two groups with regard to pre PTCA transstenotic pressure gradient (46 +/- 12 vs 42 +/- 14 mm Hg), post PTCA pressure gradient (13 +/- 7 vs 11 +/- 10 mm Hg), or post PTCA percent luminal diameter narrowing (26 +/- 18% vs 24 +/- 13%). These findings suggest that despite similar hemodynamic and angiographic improvement, the resolution of collaterals immediately after PTCA is variable.