Stereoselective increase of plasma concentrations of the enantiomers of propranolol and atenolol during exercise.

OBJECTIVE: In vitro studies have shown that, like catecholamines, both propranolol and atenolol are taken up by and released from adrenergic cells. We performed this study to investigate whether this may also play a role in humans and whether stereoselective aspects are important. METHODS: This was a randomized, double-blind, placebo-controlled, crossover study of two groups of 12 healthy volunteers. Subjects received single oral doses of 80 mg (R,S)-, 40 mg (R)-, and 40 mg (S)-propranolol; 100 mg (R,S)-, 50 mg (R)-, and 50 mg (S)-atenolol; and placebo at intervals of 1 week. Exercise was performed at 4 and 9 hours after drug intake, and blood samples were taken before and at the end of each exercise period. The plasma concentrations of the (R)- and (S)-enantiomers of propranolol and atenolol, as well as those of epinephrine and norepinephrine, were determined by HPLC. RESULTS: Effects of exercise on the plasma levels of the enantiomers of propranolol and atenolol were similar. When the optically pure enantiomers were administered, exercise caused a marked and significant increase of the plasma concentrations of the (S)- but not of the (R)-enantiomers. When the drugs were administered in the racemic form, the plasma levels of both the (R)- and (S)-enantiomers were elevated to the same extent. The increase of norepinephrine levels during exercise was more pronounced than that of epinephrine and paralleled that of the (S)-enantiomers of the beta-blockers. CONCLUSION: Bearing the in vitro data in mind, we conclude that (S)-propranolol and (S)-atenolol are taken up into and released from adrenergic cells together with norepinephrine during exercise. The reason why the plasma concentrations of (R)-propranolol and (R)-atenolol are increased only during exercise in the presence of the corresponding (S)-enantiomers remains to be determined.

Segmental degradation of left ventricular wall motion after persistent coronary fistula in a posttransplantation patient: a case report and short review of literature.

A 50-year-old man received an orthotopic heart transplant because of severe coronary heart disease and congestive heart failure. Two years after the transplantation, a continuous murmur occurred at the left sternal edge after repeated endomyocardial biopsies. Echocardiography and coronary angiography revealed a dilated left anterior descending artery with a fistula to the right ventricle. The circumflex was large with an equally postero-lateral branch, and the right coronary artery was rather small with collaterals to the distal part of the left anterior descending branch. The patient had refused any intervention to close the fistula. The left ventricular levogram was normal. Two years later, in a follow-up angiogram, the left ventricular ejection fraction had decreased as a result of hypo- and akinesis of the apex and posterior wall. We suggest that this local wall motion disturbance derives from a steal phenomenon rather than being a sequela of rejection. The decrease in left ventricular ejection fraction was associated with shortness of breath upon moderate exercise. Standard heart failure medication relieved the patient's symptoms. The observation of local wall motion disturbances in this case, as well as conflicting views in the literature, raises the question whether postbiopsy coronary fistulas in transplant patients should be closed.

Short- and long-term outcomes of Wiktor stent implantation at low versus high pressures. Austrian Wiktor Stent Study Group.

A prospective, randomized, multicenter trial was conducted to evaluate whether high-pressure postdilation of the Wiktor stent provides short- and long-term benefits compared with the conventional low-pressure implantation technique. From June 1995 through May 1996, 181 patients were randomly assigned to either low-pressure (6 to 12 atm, group A, n = 94) Wiktor stent placement or to high-pressure postdilation (> or = 13 atm, group B, n = 87) after stent deployment. All patients were followed up clinically for 7 +/- 3 months, with an angiographic follow-up in 154 patients (85%). After stent implantation, neither minimal lumen diameter (MLD) nor percent diameter stenosis (%DS) differed significantly between the 2 groups (MLD, 2.8 +/- 0.5 vs 2.9 +/- 0.5 mm; %DS, 17 +/- 8% vs 16 +/- 9% for groups A and B, respectively). However, a trend toward a larger mean lumen diameter within the stent was observed in group B (3.3 +/- 0.6 vs 3.5 +/- 0.5 mm for groups A and B, respectively; difference between means 0.14 mm, 95% confidence interval -0.01 to 0.29, p = 0.08). Angiographic follow-up revealed similar MLD and %DS in both treatment groups (MLD, 2.1 +/- 0.7 vs 2.2 +/- 0.8 mm; %DS, 31 +/- 17% vs 30 +/- 24% for groups A and B, respectively, p = NS). Acute stent thrombosis occurred in 2 patients (1%) (1 patient in each group), and subacute thrombosis in 1 patient (0.6%) in group A. There was 1 death in group A, and target lesion restenosis (> or = 50% DS) was observed in 15% of patients with no differences between the groups. In conclusion, this study demonstrated favorable short- and long-term results of Wiktor stent implantation. Despite a trend toward additional initial lumen gain by high-pressure postdilation, this did not translate into a measurable improvement in long-term outcome.

Observations on plasma ANP levels during short-term transient myocardial ischemia produced by PTCA in patients with LAD stenosis.

Ten patients with coronary artery disease and stable angina (mean age fifty-seven) were included in the study. Five of the patients had normal left ventricular function, 5 had local hypokinesia or akinesia; 8 had one-stem and 2 had two-stem disease, but all had left anterior descending (LAD) lesions ranging from 75% to 100%. Ejection fraction varied between 35% and 75% (mean 59%). Immunoreactive atrial natriuretic polypeptide (ANP) levels in the femoral vein (FV) and the coronary sinus (CS) were measured before, immediately after, and up to twenty-four hours after percutaneous transluminal coronary angioplasty (PTCA) of the LAD. ANP secretion increased by 83% (FV) and 11% (CS) within minutes after PTCA and reached control levels after thirty to sixty minutes. In patients with hypokinesia of the anterior wall, ANP secretion was significantly lower, 48% (FV) and 11% (CS) respectively. ANP secretion during PTCA was higher in patients with concomitant increase in pulmonary capillary pressure (PCP) but was also observed without an increase of PCP, suggesting ventricular ANP secretion. IN conclusion, transient myocardial ischemia leads to immediate ANP secretion even in the absence of significant pressure elevation in the left atrium. As a part of the continuous medical education program of the American College of Angiology the second part of the paper reviews the mechanisms that allow the ischemic heart to counteract the ischemic condition and thus to escape from myocardial infarction. A review of this subject is presently not available in the literature.

Evaluation of the role of coronary heart disease and left ventricular contractile function in systolic mitral valve displacement.

It has been suggested that systolic bulging of the mitral valve caused by ischaemia induced left ventricular dysfunction may ultimately lead to mitral valve prolapse, making coronary heart disease the most important cause of secondary mitral valve prolapse. The influence of coronary heart disease on systolic displacement of the mitral valve was assessed in 90 consecutive patients with chest pain who were evaluated with coronary angiography and ventriculography of the left ventricle. 22 patients had coronary heart disease affecting one vessel (one vessel disease, OVD), 35 patients had coronary heart disease affecting more than one vessel (multiple vessel disease, MVD), and 33 patients had normal coronary arteries. The prevalence of mitral valve bulging was also determined in 16 patients with dilatative cardiomyopathy (CMP). Prevalence of mitral valve bulging in patients with OVD was not significantly different from normal patients. Patients with MVD and CMP had a lower prevalence of mitral valve bulging than normal patients and patients with OVD (p < 0.001). When all patients were grouped according to their ejection fraction, regardless of their underlying disease, there was a positive correlation between prevalence of mitral valve bulging and ejection fraction (r = 0.98, p < 0.001). Patients with an ejection fraction of below 50% did not have mitral valve bulging. We conclude that coronary heart disease is not a cause of mitral valve bulging and, furthermore, that systolic mitral valve bulging may serve as indicator of good left ventricular contractile function.

Atypical Bland-White-Garland syndrome with stenosis of the origin of the left coronary artery: catheter intervention after mammary artery bypass stenosis and residual fistula to the pulmonary trunk.

A 16-year-old boy with anomalous origin of the left coronary artery from the pulmonary artery, Bland-White-Garland syndrome, underwent a mammary artery bypass grafting to the left coronary artery (LCA) together with closure of the stenosed origin of the left coronary artery. A residual LCA to pulmonary artery fistula and stenosis of the shunt at the implantation site developed that resulted in a dominant perfusion of the LCA from the right coronary artery. Interventional catheterization was performed with stenting of the LCA mammary artery anastomosis and subsequent coil occlusion of the residual fistula. After this intervention the LCA was exclusively perfused by the mammarian bypass with no residual leak to the pulmonary artery.

Seven coronary angioplasties of the left circumflex artery in a 68-year-old male.

In a 68-year-old male, seven coronary angioplasties of the left circumflex coronary artery were performed due to recurrent restenoses. Alternative approaches such as stent implantation or bypass surgery were refused by the patient.

Rescue percutaneous transluminal coronary angioplasty in a patient with a single coronary artery arising from the right Sinus Valsalvae: previously unreported scenario and review of literature.

This is the first description of treatment with coronary stenting of a patient with a single coronary artery originating from the right Sinus Valsalvae and suffering from acute inferior myocardial infarction. Angiography showed the following: the right coronary artery (RCA) had a normal course, whilst the left anterior descending (LAD) as well as the left circumflex (LCX) branches both originated separately from the proximal RCA, which served as a common mixed trunk. The LAD crossed to the left in front of the right ventricular outflow tract, whilst the LCX, taking a retroaortic course to the atrioventricular groove, had a distal occlusion. According to an anatomically based classification considering all imaginable variations, this configuration corresponds to a II-D-1 pattern, which previously has been described only in a single postmortem case. After the LCX was reopened with a guide wire, a coronary stent was successfully inserted, resulting in TIMI-3 flow. Recovery was uneventful.

Microalbuminuria is no risk factor for restenosis following percutaneous transluminal coronary angioplasty.

Microalbuminuria is known to be associated with an increased risk for cardiovascular disease. It is detectable in acute myocardial infarction and could therefore also be a risk factor for reocclusion after percutaneous transluminal coronary angioplasty (PTCA). In our study follow-up coronary angiography was performed in 50 consecutive patients with a mean age of 56 years (38-70) on average 14 months after successful PTCA. Restenosis was defined as a decrease in diameter of 25% or more of the original result and one of at least 50% in vessel diameter. In the restenosis group there were 23 patients, and 27 showed no restenosis. The family history and anamnestic risk profile, results of the initially performed coronary angiography, and laboratory risk factors were comparable in the two groups. Median microalbumin was 11.2 mg/g creatinine in those with restenosis and 9.8 mg/g creatinine in those without. Using a cut-off of 10.0 mg/g creatinine, 12 of 23 patients with restenosis (52%) and 10 of 27 patients without (37%) were positive for microalbuminuria (NS). The incidence of microalbuminuria was higher in both groups compared to historical controls. Thus, in the restenosis group the incidence of microalbuminuria tended to be higher than in the nonrestenosis group, but since this difference did not reach statistical significance, it cannot be used to predict the risk of reocclusion after PTCA.

[Abnormal origin of the ramus circumflexus sinister from the left atrium in a 30-year-old patient with aortic isthmus stenosis and atrial septal defect]. / Fehlabgang des Ramus circumflexus sinister aus dem linken Vorhof bei einer 30jährigen Patientin mit Aortenisthmusstenose und Vorhofseptumdefekt.

In this case report a 30-year-old woman suffering from progressive angina pectoris and dyspnea, having been operated on previously for atrial septum defect at the age of 19 and later aged 24 for coarctation of the aorta, is described. Upon observation, patient showed cardiac symptoms already under mild stress and remained resistant to nitroglycerin. Rest-ECG and serum cardiac enzymes were repeatedly without findings, while stress-ECG at a level of 100 W showed a ST-segment depression of 0.15 mV, at the same time complaining of angina pectoris symptoms. Coronary angiography revealed a left circumflex coronary artery arising from the left atrium being fully supplied by the left anterior descendent artery and the right coronary artery via pronounced collaterals, both originating from the ascending aorta. Despite such severe symptoms patient refused surgery suturing the abnormally arising artery. One year following coronary angiography patient is suffering from stabile angina pectoris without occurrence of myocardial infarction or another cardiovascular event.

Fibrinogen values in patients with and without restenosis following percutaneous transluminal coronary angiography.

Fibrinogen has turned out to be an independent risk factor for coronary heart disease (CHD). It is not known whether or not this parameter could be a prognostic factor for restenosis following percutaneous transluminal coronary angioplasty (PTCA), which represents the main problem limiting the long-term efficacy of this procedure. Therefore, we studied fibrinogen concentrations in a series of 50 males (mean age: 55, range: 38-70 years) with CHD and successful PTCA. Follow-up coronary angiography was performed 12 months following PTCA. Twenty-two patients had restenosis, and 28 patients were without restenosis. Both groups did not differ significantly in medical history (smoking habits, hypertension, positive family history for cardiovascular diseases), in routine lipid profile (total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, apolipoproteins A1 and B). Fibrinogen values were 405 +/- 128 mg/dl (range: 202-725) in patients with restenosis and 352 +/- 94 mg/dl (range: 187-568) in patients without restenosis (not significant). Elevated fibrinogen levels of more than 400 mg/dl were found in 8 patients in each group. Although fibrinogen is a proven marker for CHD in men, fibrinogen is not a risk factor for restenosis following PTCA.

[A 58-year-old woman with unstable angina pectoris and restenosis after PTCA: successful therapy with ketanserin]. / 58jährige Frau mit instabiler Angina pectoris und Restenose nach PTCA-Erfolgreiche Therapie mit Ketanserin.

This case report describes a 58-year-old female suffering from unstable angina pectoris showing two-stem disease with occlusion of the left anterior descending artery at angiography. Due to continuous symptoms and ECG-deviations, percutaneous transluminal coronary angioplasty of the occlusion was performed twice with primary success. However, acute re-occlusion with angina and ECG-changes developed after 6 and 2 h, respectively. For technical reasons, immediate bypass surgery was impossible and thus, patient underwent a third dilatation followed by infusion of ketanserin (0.1 mg/min), a S2-serotonergic receptor antagonist, for 24 h. During this period, patient was without complaints and showed normal ECG. Hematocrit fell and viscosity as well as elasticity improved markedly by ketanserin. Renewed angina and ECG-deviations developed 2 h after discontinuation of ketanserin therapy and patient had to undergo coronary artery bypass grafting.

Autoantibodies to oxidized low density lipoproteins in restenosis following coronary angioplasty.

Oxidized low density lipoproteins (oLDL) play an important role in the pathogenesis of atherosclerosis. Recently, elevated oLDL autoantibodies in serum were shown in patients with severe peripheral atherosclerosis. To evaluate their role in restenosis after percutaneous transluminal coronary angioplasty (PTCA), oLDL autoantibodies were determined in a randomly selected series of 48 males following successful PTCA. Follow-up angiography as well as blood sampling were done 12 months after PTCA; restenosis was defined as > or = 50% reduction in diameter of the coronary artery. Twenty-six patients (mean age: 56 years) showed restenosis (Restenosis Group), whereas 22 (mean age: 53 years) had open vessels (Patent Vessel Group). Both groups did not differ in age, past medical history, fibrinogen and lipid profile as well as in initial angiographic findings. Oxidized LDL autoantibodies were 13 +/- 21 U in the Restenosis Group and 6 +/- 4 U in the Patent Vessel Group, showing no significant difference. Six of 26 patients in the Restenosis Group and 3 of 22 in the Patent Vessel Group (NS) had elevated oLDL autoantibody levels (> or = 10 U). Thus, although there is a trend to elevated oLDL autoantibodies in males with restenosis of coronary arteries, oLDL cannot serve as a strong marker for stenosis following PTCA.

[Coronary artery anomalies in adulthood]. / Anomalien der Koronararterien im Erwachsenenalter.

In a series of 3000 consecutive coronary angiographies carried out in adults (period October 1988 through February 1991) the incidence of coronary artery anomalies was investigated. Among these there were 7.2% of patients with left-, 3.8% with right-sided and 89% with bilateral coronary artery supply. 10 cases revealed a double left anterior descendent artery (LAD), whereas in 2 patients the left circumflex artery (CX) was missing. In approximately 1% of patients origin anomalies of coronary arteries were observed, above all of the right coronary artery (RCA). A pronounced kinking of the coronaries was seen in 22 cases (11 LAD, 11 RCA) and a bridging in 2.5% of patients (74 LAD, 1 CX, 1 RCA). Of the latter, there were 21 hemodynamic active stenoses (more than 75% diameter stenosis) of which in 12 cases this narrowing was the sole cause for the heart complaints. During the same period there were 8 patients with coronary anomalies leading to shunt development out of which a 30-year-old female revealed clinically a coronary steal phenomenon. Aneurysms of the coronary arteries were observed in 54 cases (2%) whether congenital or acquired could not be ascertained. In total, there were 194 coronary anomalies in the total series (6.5%) being clinical significant in 22 cases (0.7%).

Ketanserin prevents early restenosis following percutaneous transluminal coronary angioplasty.

In the treatment of coronary artery stenoses restenosis represents the main problem in 25-35% of cases following successful percutaneous transluminal coronary angioplasty (PTCA). In the present trial the effect of the 5HT2-serotonergic receptor antagonist ketanserin on the rate of restenosis after 24 h ('early restenosis') or 4-9 months ('late restenosis') was investigated. Preliminary studies demonstrated that ketanserin infused at the dose of 0.1 mg/min inhibited platelet aggregation without evidence of side effects. In the restenosis study, 43 patients (37 males, 6 females; mean 55 years) were randomized into two groups. After PTCA, 22 patients were treated with conventional therapy (group A), whereas 21 received additionally ketanserin (0.1 mg/min for 24 h, group B). The angiograms (prior to, after, 24 h after, and 4-9 months after PTCA) were examined in a blind manner using a computer-based quantitative angiographic system. After 24 h, 3 patients of group A, but none of group B showed restenosis (more than 50% decrease in diameter stenosis). In total, the diameter at the site of stenosis prior to PTCA decreased by 11% in the controls, but remained unchanged in the ketanserin-treated patients. After 4-9 months, 26% of group A (5 out of 19 patients examined) and 22% of the controls (4 out of 18 patients examined) developed restenosis of more than 50%; there was no statistical difference in the degree of residual stenosis between both groups. These findings suggest that a 24-hour infusion of ketanserin following PTCA may prevent early restenosis, but does not influence the incidence of late restenosis.

[Coronary aneurysm in a 69-year-old patient. Transthoracic echocardiography]. / Koronaraneurysma bei einem 69jährigen Patienten. Transthorakales Echokardiogramm.

This case report is on a 69-year old male patient treated with cephalosporins because of suspected myocarditis due to borreliosis. Using transthoracic echocardiography a big aneurysm of the proximal part of the left coronary artery was detected. Coronary angiography revealed an aneurysm 1.2 cm in diameter at the origin of the left anterior descending branch and confirmed the initial diagnosis. In addition, coronary three-vessel disease with reduced left ventricular function was found. Coronaritis due to Lyme borreliosis could not be ruled out with certainty. The patient was relatively asymptomatic, and hence conservative therapy was recommended. The case described here serves as a basis for a discussion on the aetiology, clinical manifestation, diagnosis and therapeutic management of coronary aneurysms.

Intracoronary Stent Used in a Transplanted Heart.

The development of occlusive cardiac allograft vasculopathy is different from coronary artery disease in native vessels and treatment is still an unsettled problem. We describe a case of a 53-year-old male who underwent heart transplantation because of severe dilated cardiomyopathy. Based on myocardial ischemia, coronary angiography was performed six years later. Significant two-vessel coronary artery disease had developed and was treated by coronary angioplasty. Due to a suboptimal result, a Palmaz-Schatz stent was successfully implanted in the left anterior descending artery. The patency of the stent was demonstrated by ultrafast computed tomography and confirmed by control angiography three months later.