Background: Radiation therapy to the mediastinum and breast can be associated with cardiac complications. Cardiac damage may manifest early during radiation therapy or occur late, years after radiation therapy has been finished. Hypothesis: Myocardial damage is associated with the release of both troponin I (TnI) and brain natriuretic peptide (BNP). The current study sought to determine whether radiation treatment to the mediastinum and breast leads to the release of cardiac biomarkers. Methods: The study comprised 23 patients: 18 with lung cancer and 5 with breast cancer. Radiation therapy was performed for up to 6 weeks. Total radiation dose was >45 Gy in each patient with a dose of 1.8 Gy per fraction. Blood samples to determine TnI and BNP were taken before and once a week during radiation therapy. Echocardiography was done before and after radiation had been finished. Results: Two patients died during the study. Both TnI and BNP levels increased significantly during the study (log10 scale); however, absolute and mean values remained on a relatively low level (mean preradiation and postradiation TnI: 0.007 ± 0.008, 0.014 ± 0.01 ng/ml; mean preradiation and postradiation BNP: 123 ± 147, 159 ± 184 pg/ml). Conclusion: Radiation therapy leads to cardiac cell damage and changes in the left ventricular loading conditions as suggested by a significant increase of the cardiac biomarkers TnI and BNP. Determination of serum levels seems to be superior to echocardiography in detecting radiation-induced cardiac damage. Serial measurements of cardiac biomarkers may facilitate the management of patients undergoing radiation therapy and may help to define subgroups at high risk of developing heart failure.

Background: Ongoing myocardial cell damage forms the basis for progression of chronic heart failure. Evidence is accumulating that progressive loss of cardiac myocytes is associated with the release of cardiac troponin I (cTnI).Hypothesis: This study sought to determine whether levels of cTnI are of prognostic value for risk stratification of patients with chronic heart failure.Methods: Release of cTnI was measured by conventional enzyme immunoassay following serum ultrafiltration in 58 consecutive patients hospitalized for chronic heart failure and 31 healthy volunteers serving as control group. Determination of serum levels was performed every 2 weeks over a time interval of 3 months. According to the results of coronary angiography, patients were divided into Group D showing normal coronary arteries (n = 33, ejection fraction 27 +/- 6.1%) and Group I showing severe coronary heart disease (n = 25, ejection fraction 28.8 +/- 7.8%). Survival of patients was evaluated after a mean time interval of 3 years.Results: The mean cTnI serum level over all measurements was 0.66 +/- 1.8 ng/ml in patients versus 0.11 +/- 0.48 ng/ml in 41, volunteers. At all six points of analysis, the mean cTnI serum level was significantly different (p < 0.001) between patients and volunteers. There was no significant difference between patients with and without coronary heart disease following hospital discharge. however, troponin release was significantly different between survivors and nonsurvivors (n = 27) (0.56 ng/ml vs. 0.84 ng/ml, p < 0.05).Conclusion: Permanent cTnI release is a common finding in patients with chronic heart failure and a strong prognosticator. In this setting, coronary morphology seems to play a minor role for disease progression.

To determine the value of transesophageal ultrasound in the assessment of cardiac valve prostheses, 14 patients with clinically suspected mitral prosthesis malfunction were studied by transthoracic and transesophageal two-dimensional imaging as well as by color Doppler flow velocity mapping (color Doppler). Patients underwent left ventricular angiography (n = 13), surgery (n =11), or both angiography and surgery (n = 10). Nine patients had only mitral valve replacement, four patients had both mitral and aortic valve replacement, and one patient had mitral, aortic, and tricuspid valve replacement. There were 16 biological and four mechanical prostheses. The degree of mitral regurgitation was graded by both transthoracic and transesophageal color Doppler according to the area of the regurgitant jet visualized and was compared with a three-point classification of mitral regurgitation by left ventricular angiography judged by observers blinded to the echocardiographic results. All transesophageal studies were performed without complication and were well tolerated. The pathological morphology of the mitral prosthesis was additionally or more clearly visualized by transesophageal twodimensional imaging and subsequently proven at surgery in three patients with flail leaflets and one patient with a vegetation compared with images obtained by the transthoracic approach. Valvular regurgitation was graded by the transthoracic approach as absent in four patients, mild in two patients, moderate in five patients, and severe in only three patients. The transesophageal assessment showed absence of mitral regurgitation in two patients, moderate regurgitation in two patients, and severe regurgitation in 10 patients. Left ventricular angiography done in 13 of the 14 patients revealed no regurgitation in two patients, mild regurgitation in one patient, moderate regurgitation in one patient, and severe mitral regurgitation in nine patients. This corresponded to the grading by transesophageal echocardiography in 12 of the 13 patients with the 13th patient graded as mild regurgitation by angiography and moderate regurgitation by transesophageal echocardiography. We conclude that in patients with biological mitral prosthesis malfunction, transesophageal two-dimensional imaging, as well as color Doppler, can provide reliable diagnostic information beyond that available from the transthoracic approach with the degree of mitral regurgitation corresponding to that found on left ventricular angiography. (Circulation 1988;78:848-855)

INTACT (International Nifedipine Trial on Antiatherosclerotic Therapy) is a prospective, placebo-controlled, randomized, double-blind, multicenter trial analyzing the influence of 80 mg nifedipine/day on the angiographic progression of early stage coronary atherosclerosis. Coronary angiograms were taken in identical projections before and after a treatment period of 3 years. Quantitative analysis of the angiograms was performed with the computer-assisted contour detection system CAAS. For definition purposes, the coronary artery system was subdivided into 25 different segments, including all anatomic variants. Measurement parameters of segments were mean and minimal diameter, and of stenoses minimal diameter, percentage diameter reduction (at least 20%), length, and plaque area. The variable extent of the changes of these parameters in the different projections analyzed per patient in the two study angiograms was considered by separate computation of the maximal, mean, and minimal changes over these projections; the comparison of the parameter changes between the two treatment groups was performed separately according to these three modes. For all parameters, this comparison was performed on the basis of the individual 25 segments, as well as after aggregation of individual segments to arteries (RCA, LAD, and LCX), to groups of large and small segments, and to the entire coronary artery system. Assessment of changes of the coronary (patho)morphology by quantitative analysis of coronary angiograms is associated with a number of methodical limitations, which may lead to a certain variability of the results. However, due to the double-blind feature of INTACT, this variability should be comparable in the two groups of this study, allowing for a conclusive comparison.

In 26 patients with coronary artery disease, the mean diameters of angiographically 'normal' epicardial coronary arteries were assessed with the aid of a computer-assisted contour detection system (CAAS) before and up to 15 min after onset of a 4-min intravenous-infusion of 2 mg nifedipine (13 patients, group I) or 1 mg nisoldipine (13 patients, group II). Maximal coronary dilation amounted to 20 +/- 9% (4th min) in group I and to 18 +/- 9% (15th min) in group II. In addition, in group II changes of the minimal diameters of 9 coronary obstructions were measured; the maximum increase averaged 28 +/- 15% (7th min). In order to compare the pharmacokinetic properties of these compounds the dilation of the 'normal' coronary segments was correlated with the respective drug plasma levels; maximal plasma concentrations averaged 62 +/- 21 ng ml-1 (7th min) in group I and 17 +/- 7 ng ml-1 (4th min) in group II respectively. A positive, linear correlation between coronary dilation and plasma levels was only found with nifedipine (P less than 0.05); with nisoldipine, however, coronary dilation developed in form of a hysteresis curve, when plotted against plasma levels, probably due to the high receptor affinity of this substance. The prolonged efficacy of nisoldipine could be favourable in oral long-term treatment of patients with coronary artery disease.

In 396 of 423 (93.6%) patients with mild to moderate coronary artery disease participating in a coronary angiographic follow-up trial, diameters of the epicardial coronary arteries were measured with an automatic contour detection system (CAAS). The underlying INTACT study (International Nifedipine Trial on Antiatherosclerotic Therapy), a prospective, placebo-controlled, randomized, double-blind multicenter trial, investigates the influence of the calcium antagonist nifedipine (80 mg/day) on the progression of coronary atherosclerosis over a three-year interval. The study is based on coronary angiograms repeated in identical projections after premedication with 10 mg isosorbide dinitrate sublingually. For quantitative analysis the coronary artery system was, in consideration of all anatomical variations, subdivided into 25 segments. In the first angiograms of the 396 patients evaluated up to April 1, 1988, altogether 5,425 different coronary segments could be analyzed over their entire length in one or more angiographic projections--on the average 13.7 +/- 2.8 segments per patient. Analysis parameters were the mean diameters of the entire segments and of the individual subsegments (about 5 mm in length). The 10 major proximal segments could be evaluated in 76-94% of patients respectively in more than two different angiographic projections on the average; in 0-13% of patients the respective segments were occluded. In 1-4% of patients the evaluation of these segments was prevented by poor film quality and in 1-16% of patients prevented by anatomical abnormalities (e.g., segment too short or too small). 184 segments were found occluded (RCA 42%, LAD 30%, CX 28%) and 909 mostly low-grade to moderate stenoses (RCA 34%, CX 32%, LAD 30%, left main 4%) were analyzed with a special algorithm. The following obstruction parameters were derived: minimal diameter, percentage severity, length, and plaque area. The present data demonstrate that in an angiographical multicenter follow-up study such as INTACT a nearly complete quantitative morphometric analysis of the visualized coronary artery system can indeed be obtained in virtually all angiograms when a computer-assisted contour detection system is applied.

Transesophageal echocardiography is one of the new techniques available to ultrasound practitioners that uses intracavitary high-frequency phased array transducers. Transesophageal echocardiography provides diagnostic information in the patient that is difficult or impossible to image using standard transthoracic echocardiographic techniques. Presented here is an overview of transesophageal echocardiographic technique, a description of the anatomy demonstrated by using the technique, and the clinical indications for the transesophageal echocardiogram.

The effect of ionic and non-ionic contrast media on the vasomotility of epicardial coronary arteries was investigated in 21 patients during coronary angiography by use of either diatrizoate-76% (10 patients, group A) or iopromide-370 (11 patients, group B). Coronary angiograms were taken in RAO 30 degrees projection before (= reference) and directly after (t0) diagnostic angiography of the left coronary artery (approx. 7 dye injections in approx. 7 min). Additional angiograms in the same projection followed after 1, 3, 6 and 10 min. Mean diameters of angiographically normal coronary segments were analysed with an automatic edge detection system (CAAS). With diatrizoate-76% coronary dilation at t0 averaged 18.9 +/- 6.7% (P less than 0.001); it correlated positively (P less than 0.001) with the number of diagnostic injections performed per min (mean 1.2 +/- 0.3 min-1), and negatively (P less than 0.5) with the time interval between the last diagnostic contrast injection and t0 (mean interval 73 +/- 35 s). Coronary dilation was unchanged 1 min after t0 (18.3 +/- 5.4%, P less than 0.001) and was still present after 6 min (6.2 +/- 4.6%, P less than 0.01). With iopromide-370 coronary dilation at t0 was mild (5.4 +/- 4.3%; P less than 0.05); the subsequent injections led to minimal insignificant dilation. It is concluded that in quantitative angiographic studies on changes in coronary vasomotor tone repeated coronary angiograms should be taken with non-ionic contrast media; furthermore adequate injection intervals of greater than 3 min should be observed.

The diagnosis of cardiac tumors and thrombi was almost completely restricted to necropsy until echocardiography became available. Actually, the noninvasive identification of left atrial myxomas during lifetime was one of the earliest diagnostic applications of M-mode echocardiography at all [1]. Due to the rapid development in cardiac ultrasound techniques during the last 15 years, today, this method can be considered as the diagnostic approach of choice for the assessment of abnormal masses localized in and around the heart [2–7]. This is in particular true for the two-dimensional technique which allows a clear imaging of most cardiac regions. A further improvement of the imaging quality and the insight in anatomical structures which are usually not demonstrable by the transthoracic approach (as the left atrial appendage and the vena cava superior) could recently be obtained by the introduction of transesophageal echocardiography.

The diameter changes of angiographically normal coronary arteries following vasodilator drugs were studied in 41 patients. In group 1 (22 patients) angiograms and plasma levels were obtained before as well as 10, 20 and 30 minutes after 20 mg nifedipine s.l. (15 patients) or placebo (7 patients). A cluster analysis allowed a classification of patients into group A (N = 4) and B (N = 11) according to the slope of plasma level increase. Plasma levels A versus B were 27.8 +/- 9.8/13.5 +/- 4.5 ng ml-1; P less than 0.05; 54.0 +/- 11.7/21.7 +/- 6.6 ng ml-1; P less than 0.001; 79.1 +/- 9.3/28 +/- 9.8 ng ml-1; P less than 0.001. Corresponding diameter changes A versus B were: 7.3 +/- 5.1%/-5.6 +/- 9.0%; P less than 0.01; 11.4 +/- 4.1%/-4.5 +/- 11.3%; P less than 0.01; 14.5 +/- 5.9%/0.5 +/- 13.6%; P less than 0.05. In group 2 (N = 19) angiograms were obtained before as well as 2, 4, 7 and 15 minutes after administration of 10 mg isosorbide dinitrate (N = 9) or placebo (N = 10). Coronary dilation ISDN versus placebo was: 2.4 +/- 3.6%/0.9 +/- 4.0%; NS; 10.6 +/- 5.1%/3.1 +/- 3.8%; P less than 0.001; 12.3 +/- 5.9%/-0.3 +/- 6.4%; P less than 0.005; 10.5 +/- 6.5%/-4.0 +/- 7.7%; P less than 0.005. These data indicate that the interindividual variations of changes in coronary lumen size are due to different slopes of plasma level increase, most likely due to different rates of drug absorption after sublingual administration of nifedipine.(ABSTRACT TRUNCATED AT 250 WORDS)

The incidence of left atrial spontaneous echo contrast was evaluated in 52 patients with isolated or predominant mitral valve stenosis (Group 1) and 70 other patients who had undergone mitral valve replacement (Group 2). All patients were studied by conventional transthoracic and transesophageal two-dimensional echocardiography. Spontaneous echo contrast could be visualized within the left atrium in 35 Group 1 patients (67.3%) (including 7 patients with sinus rhythm) and 26 Group 2 patients (37.1%) (all with atrial fibrillation). Patients with spontaneous echo contrast had a significantly larger left atrial diameter and a greater incidence of both left atrial thrombi and a history of arterial embolic episodes than did patients without spontaneous echo contrast. Association between spontaneous echo contrast and left atrial thrombi and a history of arterial embolization (considered individually or in combination) showed a high sensitivity and negative predictive value. It is concluded that spontaneous echo contrast is a helpful finding for identification of an increased thromboembolic risk in patients with mitral stenosis and after mitral valve replacement.

In 48 patients undergoing diagnostic coronary angiography changes of mean diameters of angiographically "normal" coronary segments after intracoronary injections of diatrizoate 76% or iopromide 370 performed in different intervals, were analyzed with a computer-assisted contour detection system (CAAS). Four study protocols were applied, differing in respect to the type of contrast medium administered and/or to the timing of the reference- and control-angiograms in the course of diagnostic coronary angiography. Coronary angiograms in identical projections were performed before (= reference) and directly after (1. control = C1) diagnostic angiography of the left coronary artery by injection of either diatrizoate 76% (group 1, 10 patients) or iopromide 370 (group II, 11 patients). Additional coronary angiograms were performed 1, 3, 6, and 10 min after C1. During diagnostic angiography in either group about eight dye injections were performed in about seven min. With diatrizoate 76% a significant coronary dilation averaging 18.9 +/- 6.7% (p less than 0.001) was observed at C1, depending on the number of diagnostic dye injections performed per min (mean 1.2 +/- 0.3) and on the interval between the last diagnostic injection and C1 (mean 73 +/- 35 s). Coronary dilation persisted up to the sixth minute (6.2 +/- 4.6%, p less than 0.01). With iopromide 370 a small but significant coronary dilation was observed merely at C1 (5.8 +/- 4.3%, p less than 0.05). In two other studies coronary angiograms were performed in identical projections immediately following complete diagnostic coronary angiography (reference) and in addition after 3, 4, 5, 6, 10, and 20 min (group III, 18 patients) and after 10, 20, and 30 min, respectively (group IV, 9 patients) by administration of diatrizoate 76% as the only contrast medium. Short injection intervals (1 min) resulted in a mild coronary dilation (mean up to 2.4 +/- 4.1% compared to reference; p less than 0.05), longer intervals (3-10 min) resulted in a marked diameter reduction (averaging up to -9.7 +/- 9%; p less than 0.05), probably a consequence of the return of coronary vasomotor tone to baseline levels. These results suggest that in quantitative coronary angiographic studies (e.g., testing coronary vasomotility) non-ionic contrast media should preferably be applied, and adequate injection intervals (greater than 2 min) are mandatory. In intervention- and follow-up studies based on repeated coronary angiograms dye-induced changes of coronary vasomotor tone can be avoided by premedication with vasodilating drugs, e.g. nitrates, and/or calcium antagonists.

A number of animal studies revealed an inhibition or retardation of the progression of atherosclerosis by calcium-antagonists. Encouraged by these studies, a multicenter trial on the progression of coronary artery disease (CAD) in man was initiated testing the antisclerotic effect of nifedipine against placebo in 426 patients with mild to moderate coronary disease over 3 years. All patients underwent coronary angiography before entering the trial and will be restudied after 3 years; changes of the coronary artery lumen size are quantitatively assessed by a computer-assisted system (CAAS). INTACT (International Trial on Antiatherosclerotic Coronary Therapy) is therefore the first randomized prospective study on the progression of CAD based on a quantitated anigraphic control of the coronary system.

UNLABELLED:The diameter changes of angiographically normal epicardial coronary arteries were studied in 25 patients in correlation to nifedipine plasma levels. In group 1 (15 patients) 20 mg of s.l. nifedipine were administered. Measurements of the coronary lumen size (automated contour detection system, accuracy 0.12 mm) and detection of plasma levels (gas-chromatography) were done before and 10, 20 and 30 min after drug administration. According to the slope of nifedipine plasma levels, patients were divided into group 1 A (n = 4) and 1 B (n = 11). Plasma levels in both groups were: at 10 min, 27.8 +/- 9.8 and 13.5 +/- 4.5 ng/ml resp.; P less than 0.05; at 20 min, 54.0 +/- 11.7 and 21.7 +/- 6.6 ng/ml resp.; P less than 0.001; at 30 min, 79.1 +/- 9.3 and 28 +/- 9.8 ng/ml resp.; P less than 0.001. The corresponding diameter changes in A and B were: 7.3 +/- 5.1%/.-5.6 +/- 9.0% resp.; P less than 0.01; 11.4 +/- 4.1% and -4.5 +/- 11.3% resp.; P less than 0.01; 14.5 +/- 5.9% and 0.5 +/- 13.6% resp.; P less than 0.05. In group 2 (10 patients) 1 mg nifedipine was administered intravenously within 4 min. Measurements were done at 1 min intervals during infusion as well as 7 and 15 min after beginning and compared to a placebo group (n = 10). Peak plasma levels amounted to 16.7 +/- 5.7 ng/ml after 7 min. The maximum coronary dilation was reached after 4 min (verum 5.0 +/- 6.8%; placebo 3.2 +/- 3.6%). Significant differences between both groups were observed after 7 min (verum 4.1 +/- 5.3%; placebo -3.1 +/- 5.8%, P less than 0.05) and 15 min (verum 1.2 +/- 3.2%; placebo -6.2 +/- 8.4%; P less than 0.05).CONCLUSION:based on significantly different plasma levels following sublingual application of 20 mg nifedipine a classification of patients into "early-" and "late-coronary-responders" could be established. After intravenous infusion of 1 mg nifedipine peak plasma levels were much lower than after sublingual application of 20 mg and coronary diameters showed only a mild increase.

Among patients (pts) with coronary artery disease those with symptoms of an unstable angina pectoris form a subset particularly jeopardized with regard to threatening myocardial infarction (MI) or cardiac death (CD). We analyzed over 5.4±2.1 years (Y) the clinical course of 123 pts, who between 1977 and 1982 had to be admitted to the intensive care unit for reasons of persisting angina at rest. Within the first 24 hours no patient revealed a significant elevation of serum creatine kinase or typical alterations in the ECG due to acute MI (new Q-waves). During their stay in hospital (19±17 days) 43 pts (37 men, 6 women; age 58±7 Y) were subjected to bypass graft surgery, 80 pts (60 men, 20 women; age 58jh10 Y) were medically treated, 13 of whom underwent subsequent bypass graft surgery because of aggravation of symptoms. The table presents a survey of cardiac mortality and incidence of MI in the collectives with medical and surgical treatment during the stay in hospital and 1, 3 and 5 Y after dismissal (calculated according to the life-table method of Kaplan-Meier). Hence, during the initial hospitalization infarction and mortality rate in the medically treated group indeed were smaller than in the surgical collective; however, after dismissal this beneficial mortality rate turned into the opposite in the course of the following years. In this group nearly every MI was fatal.