Jochen Thormann

Effect of coronary collaterals on left ventricular function at rest and during stress

Abstract The influence of coronary collateral vessels on resting left ventricular function was investigated in 87 consecutive patients with complete coronary artery occlusion of at least one of the three major coronary vessels. The morphology of coronary and collateral circulation was evaluated by coronary arteriography. Left ventricular function was assessed by biplane ejection fraction and segmental wall motion was evaluated by hemiaxes shortening. Collaterals to occluded arteries were graded as good or poor, according to the caliber of the distal vessel segment. Patients were divided into those with good collaterals (n =35), and those with poor or absent collaterals (n = 52), furthermore, these two groups were subdivided according to the location of coronary artery occlusion. Collateralized single vessel occlusions were found more frequently than collateralized multiple vessel occlusions. Ejection fraction and segmental wall motion was significantly better in well collateralized occlusions than in poorly collateralized occlusions of LAD or RC and was normal or depressed only slightly if compared to 17 patients without heart disease. In contrast, total and regional myocardial function was severely depressed in poorly collateralized LAD or RC occlusion. Ventriculography after rapid ventricular pacing was performed in 12 of 87 patients with well collateralized or poorly collateralized LAD occlusion to evaluate to what extent coronary collaterals protect anterior wall motion during increased oxygen demand. Pacing induced a drastic fall of anterior wall motion in well collateralized segments whereas no change was found in poorly collateralized segments. Reviewing clinical data of two patient groups with comparable numbers and locations of occlusions revealed in the well collateralized group more severe angina (p

Thrombotic complications with pacemakers

To analyze thrombotic complications, we performed brachial phlebographies in 100 consecutive patients (group 1), about 44 months after permanent pacemakers had been installed. Thirty-nine patients showed thrombotic lesions in the veins used to pass the stimulation electrode into the right ventricle. In 10 patients the medical history and in 12 patients clinical symptoms and signs indicated an impairment of venous flow. Fifteen of the 39 patients showed complete occlusion of one venous segment; collateral vessel formation was found dependent on the site and the extent of the occlusion. In the remaining 24 patients only partial occlusion without collateralization was demonstrated. Group 2 comprised 12 patients in whom the pacing lead originally inserted via right-sided veins had been severed and the free distal end left unsecured intraluminally when the second electrode was inserted via the left-sided cephalic vein. In all these patients phlebography about 19 months later revealed thrombotic complications, while 11 presented with clinical symptoms and signs. The incidence of thrombotic complications including segmental occlusion after the application of permanent pacer leads is only one-third of patients with segmental occlusion symptoms. However, since severed leads produce severe symptomatic complications in almost all cases their removal is mandatory.

Effectiveness of nicorandil (SG-75), a new long-acting drug with nitroglycerin effects, in patients with coronary artery disease: improved left ventricular function and regional wall motion and abolition of pacing-induced angina.

Summary Nicorandil (SG-75; SG), 2-nicotinamidoethyl nitrate, is a new antianginal drag with coronary dilatory properties, according to investigations conducted in Japan. In nine patients with coronary artery disease and with reproducible pacing-induced myocardial ischemia, the effect of SG, 20 mg sublingually, was studied, i.e., changes in heart rate, arterial pressure, angiographic left ventricular (LV) ejection parameters, contractility, LV function, LV work, myocardial oxygen consumption, cardiac efficiency, and regional wall motion for the following hemodynamic phases were investigated at the 7th and 14th min after SG, the immediate postpacing phase without medication, and the postpacing phase under the influence of SG. There was no change as compared with control values (p > 0.05) in the 7th and 14th min after SG application and without stress. In the 15th and 16th min post-SG (serum level control), under equipotent pacing stress, myocardial ischemia could no longer be elicited, as, however, had been the case in the postpacing period without medication. In addition, percentile parameter changes (p < 0.05) comparing the postpacing phase, with SG, with the postpacing phase, without medication, were as follows: ejection fraction, +21%; cardiac index, +37%; stroke work index, +48%; LV work, +52%; cardiac efficiency, +60%; and regional wall motion, improved. “Protection from ischemia” and improved hemodynamics under SG influence were probably mainly due to a decrease in preload (left ventricular end-diastolic pressure, by −41%) and afterload (systemic vascular resistance, by −29%). These parameter changes correspond to alterations that could have been expected theoretically also after nitroglycerin given under similar conditions. Because, in addition, no untoward effects, either subjective or objective, could be elicited during or after application of SG, this seems to be a promising drug for antianginal therapy of the future.

Progressive cardiac involvement by Fabry's disease despite successful renal allotransplantation

Enzyme replacement by renal allotransplantation has been suggested as a specific mode of therapy for Fabrys disease. We report a case of Fabrys disease who developed symptoms and signs of heart failure despite successful renal transplantation 14 years ago. Echo- and angiocardiographic features resembled findings in patients with hypertrophic non-obstructive cardiomyopathy. Endomyocardial biopsy specimens demonstrated cardiac manifestation of Fabrys disease.

Tedisamil (KC 8857) is a new specific bradycardic drug: does it also influence myocardial contractility? Analysis by the conductance (volume) technique in coronary artery disease.

To determine whether inotropism influences the bradycardic action of tedisamil, hemodynamic assessment was performed in 13 patients with ischemic coronary artery disease including analysis of end-systolic pressure-volume relationships after an infusion of tedisamil, 0.3 mg/kg, at rest, and during paced tachycardia stress. Slope Emax fell by 14% at rest (13 patients) and by 10% during tachycardia (6/13 patients), whereas loops of end-systolic pressure-volume relationships moved rightward; all parameter changes indicated a lack of significant inotropism loss with tedisamil (p > 0.05). Although the mean heart rate decreased from 77.5 to 64.7 beats/min and QTc duration increased by 14% (p < 0.05), filling pressure and dp/dtmin remained unchanged and vascular resistance increased by 30%. Parameters of left ventricular pump function (ejection fraction, stroke volume, left ventricular efficiency) decreased slightly (between 3% and 13%), whereas left ventricular volumes increased (end-diastolic volume by 6%, end-systolic volume by 23%). The respective parameter changes during tachycardia were comparable in tendency, and angina could no longer be induced during postdrug pacing stress. We concluded that the bradycardic effects of tedisamil are selectively generated without impairing either ventricular pump function or contractility in a clinically relevant fashion, whereas the postdrug anginal threshold appears elevated. Thus tedisamil can be used safely in ischemic coronary artery disease.

Vagal tone, significance of electrophysiologic findings and clinical course in symptomatic sinus node dysfunction

Abstract The relation of hypersensitive carotid sinus syndrome (HCSR) to sick sinus syndrome (SSS) is not clear; vagal role, relevance of electrophysiological testing, and the natural course of both syndromes are ill defined. In 186 symptomatic patients, resting heart rate (HR), carotid sinus pressure results (CSP), and corrected sinus node recovery time (CSRT) were determined before and after atropine (A). According to test results 102 patients had HCSR (group I), 33 had HCSR + SSS (group II), 30 patients had isolated SSS (group III) and 20 served as control (group IV). HR below 60 b.p.m. in groups I to III and lower than controls (p 0.05), which implies increased vagal tone in HCSR but destructive affection of the SA node in SSS. Bradycardia, S-A block, supraventricular tachyarrhythmias and the combination of dizziness and syncope served as diagnostic clues for HCSR or SSS in a limited number of patients. CSP and CSRT separated HCSR from SSS but failed to predict syncope in groups I to III (p > 0.05) and thereby cannot aid the indication for pacer application. SSS test results remained unchanged over 16 months showing an unfavorable prognosis. We conclude that HCSR and SSS, although frequently occurring together, are entities made separate by specific testing, which, however, fails to aid in therapeutic decision-making. Vagal tone plays but one role in HCSR and SSS and electrophysiologic pathology of SSS does not improve in its course.

Hemodynamic, antiischemic, and neurohumoral effects of enoximone in patients with coronary artery disease.

To evaluate the risk of ischemia in 17 patients with significant coronary artery disease, the influence of enoximone was analyzed under the following conditions: (1) at rest (RC) and during exercise (ExC) under control conditions and (2) at rest (RE) and during exercise (ExE) after administration of enoximone (0.75 mg/kg, intravenously). During ExC all patients had ischemia (angina, and ST segment alterations); metabolic markers of ischemia (MMI) increased, as did the mean pulmonary artery pressure, from 19 to 41 mm Hg. However, during ExE ischemia was abolished (no angina, decrease in mean pulmonary artery pressure to 24 mm Hg, and improvement in MMI) and there was some improvement in left ventricular pump function, whereas pre- and afterload decreased (pulmonary artery pressure by 40%, systemic vascular resistance by 10%), and heart rate, arterial pressure, and myocardial oxygen consumption (MVO2) were all unchanged (p greater than 0.05). Comparative hemodynamics at RE vs RC showed a decrease in pulmonary artery pressure (by 25%) and pulmonary vascular resistance (by 19%) and an increase in heart rate (by 11%), whereas arterial pressure and MVO2 were unchanged (p greater than 0.05). Enoximone did not induce changes in plasma catecholamine, prostaglandin, or thromboxane levels (p greater than 0.05), whereas the atrial natriuretic factor decreased (by 15%), probably because of unloading of the atria during exercise. We concluded that enoximone induces beneficial hemodynamic effects in coronary artery disease without causing ischemia, probably by enhancing myocardial contractility, vasodilation, and improved diastolic properties.

Effects of AR-L 115 BS (Sulmazol), a new cardiotonic agent, in coronary artery disease: Improved ventricular wall motion, increased pump function and abolition of pacing-induced ischemia

AR-L 115 BS (Sulmazol) is a new noncatechol, nonglycosidic cardiotonic agent. In 17 patients with significant coronary artery disease, the influence of AR-L 115 BS on hemodynamics and regional wall motion was investigated under the following conditions: 1) control, 2) the immediate postpacing period without medication, and 3) the postpacing period under the peak influence of AR-L 115 BS, 2 mg/kg intravenously. During the postpacing phase without medication, all patients developed ischemia (angina, ST segment alterations, increase of mean left ventricular end-diastolic pressure from 13 to 30 mm Hg), left ventricular pump function diminished and overall regional wall motion showed a tendency to decrease (p greater than 0.05). However, during the postpacing period with AR-L 115 BS medication, ischemia was abolished (no angina; mean left ventricular end-diastolic pressure decreased to 13 mm Hg; hemodynamic variables returned to control levels and left ventricular pump function showed some improvement while overall regional wall motion showed tendencies to improve. A comparison of alterations of hemodynamics and regional wall motion during the postpacing phase without medication with those under the influence of AR-L 115 BS shows that overall left ventricular pump function and regional wall motion improved while angina and an increase in left ventricular end-diastolic pressure were prevented. It is concluded that AR-L 115 BS improves left ventricular pump function and regional wall motion in coronary artery disease without inducing ischemia, probably by means of a reduction in extravascular resistance.

Hemodynamic and myocardial energetic changes induced by the new cardiotonic agent, AR-L 115, in patients with coronary artery disease

AR-L 115 has been shown to improve left ventricular (LV) pump function in patients with advanced congestive cardiomyopathy by the intravenous and oral routes. Since AR-L 115 effects on myocardial oxygen consumption (MVO2) and coronary blood flow (CSF) are unknown, the hemodynamic, myocardial metabolic, and ECG responses to AR-L 115 (2 mg/kg bolus) were monitored at 9-, 14-, and 9-minute intervals in seven patients with coronary disease, exhibiting ischemia during pacing stress only. Maximal responses occurred at the fourteenth minute after AR-L 115. There were (average) increases in cardiac index by 30%, heart rate by 19%, CSF by 39%, MVO2 by 34%, and LV dp/dt max by 27%. There were (average) decreases in peak LV systolic pressure by 13%, LV end-diastolic pressure by 42%, systemic vascular resistance by 34%, and in coronary vascular resistance by 37%. All changes were significant (p less than 0.05). Myocardial lactate extraction, stroke work index, and stroke index remained unchanged (p greater than 0.05). The modest increase in MVO2 is possibly explained by the increase in contractility being partially offset by reductions in LV preload and afterload. AR-L 115-improved LV pump function was accompanied by moderate increases in MVO2 and CSF but without evidence of myocardial ischemia.

Present use of positive inotropic drugs in heart failure.

Cardiac failure is treated with increasing success by phosphodicsterase-III (PDE-III) inhibitors such as amrinone. milrinone. and enoximone. While relatively pure positive inotropic substances (e.g., dopamine and dobutamine) are limited by tolerance development and MVO2 increase, the efficacy of PDE inhibitors is maintained by avoiding catecholamine and β-reeeptors. They have positive inotropic, positive lusitropie. and vasodilatatory properties: myoeardial oxygen consumption remains unaltered. PDE-III inhibitors act by selectively inhibiting PDE-III. leading to an increased cAMP concentration in myoeardial and smooth muscle cells. In contrast, forskolin increases intracellular cAMP by activation of adenylate cyclase. It could be shown that parenteral administration of the PDE inhibitors sulmazole. amrinone. and enoximone resulted in preload and after-load reduction due to vasodilation with concomitant decrease of peripheral and pulmonary vascular resistance: they also led to elevated cardiac output and ejection fraction as well as a significant increase in dp/dtmav. while left ventricular filling pressures were markedly lowered. Pulmonary pressure values fell significantly, whereas heart rate and myoeardial oxygen consumption showed no clinically relevant alterations. In patients with angiographi-cally documented coronary artery disease, the anti-is-chemic efficacy of enoximone could be proven both during exercise and stress pacing. The decrease of the pathologically elevated pulmonary pressures during ischemia was accompanied by reduced ST-segment depression following enoximone without changing MVO2 significantly. First tests after intracoronary application of enoximone confirmed its direct myoeardial efficacy, indicating its positive inotropic and lusitropie properties. Thus, patients in cardiac failure have useful therapeutic alternatives at their disposal when taking PDF. inhibitors. The anti-isehemic properties of these drugs need further evaluation