Showing papers in "European Heart Journal in 1989"

Factors influencing the presence or absence of acute coronary artery thrombi in sudden ischaemic death

Abstract: Sudden ischaemic death results either from an episode of acute myocardial ischaemia consequent upon coronary thrombosis or from an arrhythmia arising within a scarred left ventricle. Very different proportions of these two groups have been reported in both clinical studies in resuscitated subjects with out-of-hospital ventricular fibrillation, and in necropsy series. In 168 cases of sudden death due to ischaemic heart disease coming to necropsy 73 (43.5%) had mural intraluminal coronary thrombi, 50 (29.8%) had occlusive intraluminal thrombi, and 45 (26.7%) had no intraluminal thrombi, giving a ratio of 2.7:1 for those with and without coronary thrombosis. Single vessel disease, the presence of acute infarction at autopsy and prodromal symptoms were positively associated with the presence of coronary thrombosis. Conversely, the presence of old myocardial infarction at necropsy, a known clinical history of ischaemic heart disease and triple vessel disease were associated with the absence of acute thrombosis. The reported variation in the incidence of coronary thrombi in sudden ischaemic death can be largely explained by selection of subjects with those clinical characteristics which are positively or negatively associated with coronary thrombosis.

Heart rate variability in relation to prognosis after myocardial infarction: selection of optimal processing techniques.

Abstract: Automatic analysis of heart rate variability from Holter recordings may be invalidated by beat recognition errors and recording artefact, necessitating filtering and editing of the computer-recognized RR interval sequence. Two new methods for heart rate variability analysis have been developed, based on an estimation of the width of the main peak of the frequency distribution curve of the computer-recognized normal-to-normal beat sequence. These methods are independent of a low level of recognition error and artefact, thus removing the need for operator-dependent, time-consuming editing. The value of the new methods (heart variability indices 1 and 2) in identifying patients with serious events (death and symptomatic, sustained documented ventricular tachycardia) during a 6-month follow-up after acute myocardial infarction was assessed in a case-control study comparing 20 patients who had experienced such events (Group I) with 20 patients who, following admission with acute myocardial infarction, had remained free of complications for greater than 6 months after discharge (Group II). Group II was selected to match Group I with regard to age, sex, infarct site, ejection fraction, and beta-blocker treatment. Analysis of the unfiltered computer-recognized normal-to-normal interval sequence showed that heart rate variability indices 1 and 2 were significantly lower (P less than 0.005, P less than 0.002) in those who had experienced events compared with those free from complications. Two other methods of expressing heart rate variability, including the standard deviation method, in combination with four different data-filtering techniques, gave less significant distinction between those with and without events during follow-up. It is concluded that using the methods described, reduced heart rate variability in patients at risk from death or sustained ventricular tachycardia after acute myocardial infarction can be detected automatically from unfiltered Holter tape recordings even in the presence of a low level of beat recognition error and recording artefact.

The European Cooperative Study on the clinical significance of right heart thrombi

Abstract: Information on a total of 119 patients with echocardiographically detected right heart thrombi was collected by questionnaire. Two major thrombus types with different morphology, etiology and clinical significance were identified: (1) 48 patients had long, thin, extremely mobile thrombi which resembled a worm or a snake (type A); (2) 57 patients had more or less immobile, non-specific clots resembling left heart thrombi (type B). Type A patients had a high incidence of deep venous thrombosis and a low incidence of potentially thrombogenetic cardiac abnormalities. The reverse was true for group B. These observations and the peculiar worm-shape of type A thrombi suggest that most type A thrombi originate in peripheral veins, while most type B thrombi develop within the right heart chambers. Clinically, type A patients were a high-risk group;pulmonary embolism was the rule andwas usually severe. Early (≤8 days) thrombus-relatedmortality was excessively high (42%), including 13 deaths from pulmonary embolism, one from paradoxical peripheral embolism and six peri-operative deaths. Type B thrombi were much more benign;pulmonary embolism was not uncommon (40%) but never fatal. Early thrombus-relatedmortality was only 4% (two peri-operative deaths). Fourteen cases could not be classified as A or B because their thrombi were highly mobile (= not B) but not worm-shaped (= not A). This small group was intermediate between groups A and B in all respects. An analysis of the relationship between therapy and outcome revealed that type B thrombi had a good prognosis irrespective of the treatment. In type A cases early thrombus-related mortality was much lower with surgery (27%) than with conservative treatment (54%). However, the selection of surgical cases was certainly very biased and it is not clear to what extent the better results of surgery are caused by patient selection. Thus the optimal management of these cases remains to be determined.

Risk factors for heart failure in the general population: The study of men born in 1913

Abstract: In 1963 a sample of 973 men, all 50 years old, was drawn from the population register of Gothenburg, Sweden. These men have been followed up for 17 years with repeated examinations regarding a number of variables possibly related to cardiovascular disease. The latest examination, at the age of 67 years, focused on congestive heart failure (CHF). The incidence rate of manifest CHF varied from 1.5 to 10.2 cases (1000 population)-1 yr-1, depending on which age group was being studied. For the age group 50-67 years the incidence of manifest CHF was 5.5 (1000)-1 yr-1. A large number of factors associated with the risk of acquiring CHF were identified. In multivariate regression analyses, hypertension and smoking were the major independent risk factors. Body weight, heart volume, T-wave abnormalities, heart rate variability, peak expiratory flow rate, psychological stress and Fy-antigen (a genetic marker?) were also independent risk factors. Possible strategies for prevention are discussed.

Evidence for increased levels of plasminogen activator inhibitor and tissue plasminogen activator in plasma of patients with angiographically verified coronary artery disease

Abstract: SUMMARY We studied 234 consecutive patients who underwent coronary angiography because of severe angina pectoris. Tissue plasminogen activator (tPA), plasminogen activator inhibitor (PA1), and lipoprotein Lp(a) were measured in citratedplasma samples. The 214 patients showing significant coronary artery stenosis (>50% reduction of luminal area in any of the great coronary arteries) had higher mean levels of tPA (P <0.001) and PAI (P <0.01) than a random population sample of similar age. PAI and tPA levels were higher in smokers than in either non-smokers or ex-smokers, and in patients with hypertension tPA was increased. Subjects with blood group A had a higher mean Lp(a) level than subjects with blood group O. There were positive correlations of PAI and tPA levels with serum triglycerides and with body mass index; Lp(a) correlated weakly with plasma fibrinogen concentrations. The findings suggest an impairment of the fibrinolytic system in patients with coronary artery disease, which offers a link between established risk factors and a plausible pathophysiological mechanism, namely thrombus turnover.

Dipyridamole-echocardiography test: historical background and physiologic basis

Abstract: Dipyridamole was first introduced as an antianginal, coronary vasodilator agent. It was soon found that this drug could not prevent effort ischaemia; on the contrary, given intravenously, it could frequently induce ischaemia in the presence of coronary artery stenosis. This property was exploited for the diagnosis of coronary artery disease. The dipyridamole–induced ischaemia was detected by different techniques: ST–segment depression, thallium 201 scintigraphy and echocardiography. This review article describes the mechanisms underlying dipyridamole–induced ischaemia and discusses the value of this pharmacologic stress test for the detection of coronary artery disease.‘Life must be lived going ahead, but it can be understood only coming back’ (Soren Kierkegaard).

Spectral mapping of the electrocardiogram with Fourier transform for identification of patients with sustained ventricular tachycardia and coronary artery disease

Abstract: In time domain analysis, detection of late potentials is limited by high pass filtering, noise interference and the necessity to exclude patients with bundle branch block. We therefore used frequency analysis with Fourier transform of multiple segments of the surface electrocardiogram (25 segments, size 80 ms, time shift 3 ms) during sinus rhythm after signal averaging. Thirty-two post-myocardial infarction patients with sustained ventricular tachycardia (VT), 19 post-myocardial infarction patients without VT and 17 healthy subjects were studied. A total of 18 patients had bundle branch block. In 24 out of 32 patients with VT, three-dimensional spectral plots were characterized by spectral peaks greater than 10 dB in the range of 40-200 Hz in segments only at the end of QRS and the early ST wave, but not far outside the QRS. In only 2 out of 19 patients without VT and in 1 out of 17 healthy subjects could such peaks be observed. Noise caused spectral peaks throughout all segments. Sixteen out of 18 patients with bundle branch block were correctly classified with spectral mapping. With the Simson method, patients with bundle branch block had to be excluded, abnormal results were found in 10 out of 19 patients with VT, but also in 5 out of 15 patients without VT and in 3 out of 16 healthy subjects. Thus, spectral mapping of the electrocardiogram offers promise for better identification of patients prone to sustained VT in the presence of coronary artery disease.

Effects of metoprolol on mortality and late infarction in diabetics with suspected acute myocardial infarction. Retrospective data from two large studies

Abstract: From two large scale studies in patients with suspected acute myocardial infarction we report the outcome in diabetics after treatment with either metoprolol or placebo. In the Goteborg Metoprolol Trial mortality at 3 months was reduced by metoprolol from 17.9% to 7.5% and late infarction was reduced from 16.4% to 3.8%. In the MIAMI Trial, mortality was decreased by metoprolol from 11.3% to 5.7% and the occurrence of late infarction was decreased from 4.5% to 3.1% during 15-day follow-up. Compared with the overall results, the effect of metoprolol on mortality appears particularly impressive in diabetics.

Radiofrequency coagulation of ventricular myocardium: Improved prediction of lesion size by monitoring catheter tip temperature

Abstract: To assess the importance of voltage, current, impedance and catheter tip temperature for the prediction of the size of tissue injury induced by transcatheter radiofrequency application, radiofrequency pulses (500 kHz) were delivered both in vitro and in vivo to isolated ventricular preparations and the intact canine heart, respectively. Radiofrequency coagulations were performed using unipolar electrode configuration. Besides measurements of current and voltage which were used to calculate the delivered power and tissue impedance, the catheter tip temperature was monitored during each application using specially designed 6F USCI catheters with a built-in nickel/chromium-nickel thermoelement. Lesion dimensions were measured and the correlation between lesion volume and delivered radiofrequency energy, maximum changes in catheter tip temperature and the integral of the temperature curve were calculated. First, in a pilot in vitro investigation, 50 radiofrequency coagulations (3.2 W-22.4 W, pulse duration 10 s) were performed in ventricular preparations from freshly excised dog hearts. The correlation between applied radiofrequency energy and lesion volume was 0.87; the correlation between maximal catheter tip temperature and lesion volume was 0.82; the correlation between temperature integral and lesion volume was 0.9. In the intact dog heart, 44 radiofrequency pulses were delivered to the left and right ventricular endocardium in 12 anaesthetized dogs (exposure time: 10 s). Delivered power ranged between 5.6 W and 24.6 W; tissue impedance varied between 92 omega and 364 omega; lesion volume measured 0-273 mm3; developed peak temperatures ranged from 16.25 degrees C to 196 degrees C. The calculated integral beneath temperature curves measured 126-1971 degrees C.s. The correlation between applied radiofrequency energy and lesion volume was 0.32; the correlation between maximal catheter tip temperature and lesion volume was 0.61. Temperature integral correlated best with the assessed volume of myocardial necrosis (r = 0.7). No significant arrhythmogenic or haemodynamic side-effects were observed. Macroscopic examination showed a central depression surrounded by a zone of homogeneous coagulation. Vaporization and crater formation up to a depth of 4 mm were observed following three radiofrequency discharges. In two of these cases, rapid changes and oscillation of catheter tip temperature were observed. Thus, monitoring of catheter tip temperature during radiofrequency energy application improves the prediction of lesion size. In addition, temperature monitoring might improve the safety of the procedure with respect to the risk of perforation.

A comparison of the effects of adrenaline and noradrenaline on human heart: the role of beta 1- and beta 2-adrenoceptors in the stimulation of adenylate cyclase and contractile force.

Abstract: The stimulant effects of adrenaline and noradrenaline on contractile force and adenylate cyclase, mediated through beta 1 and beta 2-adrenoceptors, are analysed in isolated atrial and ventricular myocardium of man. The tissues were obtained from patients without advanced heart failure undergoing heart surgery. Usually, both adrenaline and noradrenaline stimulated adenylate cyclase predominantly through ventricular and atrial beta 2-adrenoceptors. Because the relative density of beta 2-adrenoceptors is usually smaller than that of beta 1-adrenoceptors, stimulation of one beta 2-adrenoceptor leads to the production of up to 10 times more cyclic AMP molecules than does stimulation of one beta 1-adrenoceptor. Adrenaline and noradrenaline maximally enhance contractile force through both atrial and ventricular beta 1-adrenoceptors. Adrenaline can also maximally enhance contractile force through atrial beta 2-adrenoceptors. In the ventricle, adrenaline increases force via beta 2-adrenoceptors by up to 60% of its maximal beta 1 response. Noradrenaline can increase atrial and ventricular contractile force through beta 2-adrenoceptors but only at high concentrations. Unexpectedly, in atria from patients treated with the beta 1-selective antagonist atenolol, contractile responses to adrenaline are markedly and selectively augmented through activation of beta 2-adrenoceptors. In atria from atenolol-treated patients equi-inotropic concentrations of adrenaline and noradrenaline acting through beta 2 and beta 1-adrenoceptors, respectively, cause similar increases of cyclic AMP and of cyclic AMP-dependent protein kinase activity.

The future of saphenous vein as a coronary artery bypass conduit

Abstract: Continuing widespread use of autologous saphenous vein for coronary artery bypass grafting seems unavoidable despite its poor-term patency. We review here the evidence that platelet activation is responsible for early and late vein graft occlusion and conclude that other mechanisms probably contribute to late occlusions. We suggest that a rational strategy to improve vein graft patency should include: improved endothelial preservation during surgical implantation; use of better antiplatelet agents, in particular those which prevent platelet adhesion as well as aggregation; reduction of risk factors including serum cholesterol; and application of agents (e.g. heparin) which inhibit smooth muscle cell proliferation directly. We draw parallels between the pathogenesis of vein graft occlusion and coronary atherosclerosis and suggest that testing strategies for improving vein graft patency may also shed light on atherogenesis.

Increased mortality in men with ST segment depression during 24 h ambulatory long-term ECG recording

Abstract: 'Men born in 1914', from Malmo, Sweden, is a cohort study of the morbidity and mortality of cardiovascular diseases among 68-year-old men in an urban population. Ambulatory long-term ECG recording was part of the health examination that these men were invited to undergo in 1982. Five hundred attended (80.5%) of the 621 invited. Ninety-eight of the 394 men in whom the ECG recording was technically satisfactory had at least one episode with horizontal or downsloping ST segment depression greater than or equal to 0.1 mV. The median total duration of ST segment depression was 135 min. 90% of these episodes were not preceeded by any increase in heart rate. In only eight of the 47 men who reported an occurrence of chest symptoms during the recording period did ST segment depression and chest symptoms occur simultaneously. 43 months after the health examination, 33 (8.4%) men had died. The mortality in men without ST segment depression and without any history of coronary heart disease was 6.5%. The incidence of fatal and non-fatal myocardial infarction in men without ST depression greater than or equal to 0.1 mV and without a history of IHD was 2.3%. Men with ST depression greater than or equal to 0.1 mV in comparison with this group had a 4.4 times greater relative risk. The risk in men with both ST segment depression greater than or equal to 0.1 mV and history of coronary heart disease was 16.0 times greater. This study shows that asymptomatic ST segment depression is a frequent finding in elderly men. The occurrence of asymptomatic ST segment depression is associated with an increased cardiovascular mortality. This increased mortality is independent of a history compatible with angina pectoris or previous myocardial infarction.

Long-term follow-up in patients with arrhythmogenic right ventricular disease

Abstract: Follow-up was obtained in 33 of 35 patients with arrhythmogenic right ventricular disease (ARVD) from three centres, one in France, and two in the United States. The majority of patients are living but require antiarrhythmic drug therapy. Analysis of syncope as a prognostic factor for arrhythmic death in this series, as well as in patients with ARVD reported in the literature, suggests a more favourable long-term prognosis in those patients who did not have a history of syncope. ARVD may be due to a variety of pathological entities and the prognosis of patients who have different aetiologies may well be distinct from one another.

Thoracic epidural anaesthesia in patients with unstable angina pectoris

Abstract: The effect of high thoracic epidural anaesthesia with intermittent epidural bolus injections of bupivacaine (2.5 or 5 mg ml-1) was studied in 28 patients with unstable angina pectoris. The majority of the patients had a history of previous acute myocardial infarction(s) and/or angina pectoris and severe coronary artery disease. All patients were treated with nitroglycerin infusion for greater than 24 h and were included in the study if they had chest pain, not caused by acute myocardial infarction, at bed rest or recurrent anginal pain at rest greater than 2 days after infarction. 4.4 +/- 0.3 ml of bupivacaine induced a blockade of the upper seven sympathetic segments (Th1-7) for 98 +/- 9 min. Heart rate decreased significantly from 70 +/- 3 to 64 +/- 3 beats min-1 while blood pressure was unaffected by thoracic epidural anaesthesia. In 27 patients (96%) the anaesthesia induced complete analgesia. Nitroglycerin infusion was discontinued definitely within 3 h in 26 patients (93%) and pain was thereafter controlled by means of thoracic epidural anaesthesia as the sole treatment in 23 patients (82%) and as the major treatment in 25 patients (89%). Twenty-one patients (75%) were fully mobilized and stabilized. Treatment with thoracic epidural anaesthesia lasted for 6.0 +/- 1.1 days. The number of daily epidural injections decreased significantly with time from 2.7 +/- 0.3 the first day to 0.9 +/- 0.3 the fourth day (P less than 0.01, n = 19). Two patients developed acute myocardial infarction during the anaesthesia treatment period, and one of these patients died.(ABSTRACT TRUNCATED AT 250 WORDS)

Stenting of coronary arteries. Are we the sorcerer's apprentice?

Abstract: Stenting of coronary arteries following coronary angioplasty may have a role in relieving procedure-related abrupt occlusion and in the reduction of late intimal hyperplasia responsible for “restenosis”. In the period from March 1986 to January 1988, the initial 117 Wallstent endovascular devices were implanted in the native coronary arteries or saphenous vein bypass grafts in 105 patients. Follow-up angiograms (mean 5.3 ± 4.3 months) were obtained in 86 patients with 96 stents and analyzed quantitatively by a computer assisted cardiovascular angiographic analysis system. Complete occlusion occurred in 25 stents in 25 patients (26%), with 22 of these occlusions documented within the first 14 days. In the 71 remaining patent stents, there was a significant improvement in minimal luminal diameter (MLD) and percentage diameter stenosis (DS) immediately following stenting (1.9 ± 0.4 mm to 2.6 ± 0.5; 36 ± 11% to 19 ± 7%, respectively, p < 0.001). However, there was significant late reduction in MLD and increase in mean DS in the stented segment to 2.3 ± 0.8 mm and 31 ± 16% at follow up (p <0.002). Despite this late angiographic narrowing, MLD and DS remained superior to the immediate post-angioplasty result (p < 0.002). Significant hyperplasia, defined as a change in minimal luminal diameter ⩾0.72 mm or increase in diameter stenosis to ⩾50%, occurred in 30% and 14% of stents, respectively. We conclude that early occlusion remains a significant limitation with this particular coronary stent. Although hyperplasia occurs in a significant number of stented lesions, the early intrinsic dilating function of the stent appears to attenuate the effects of this process.

Quality of life five years after myocardial infarction

Abstract: In 539 patients 5 years after myocardial infarction (MI), quality of life and factors influencing life quality were studied. All patients originally participated in an early intervention trial with ...

Fatal outcome associated with autopsy proven myocardial bridging of the left anterior descending coronary artery.

Abstract: Two patients with myocardial bridging of the left anterior descending coronary artery associated with myocardial infarction are described. One of them died from acute cerebral emboli related to cardiac thrombosis in a left ventricular aneurysm. The other died suddenly while sleeping. Both patients were found to have a very long myocardial bridging of the left anterior descending coronary artery as well as patches of fibrosis in the left anterior descending coronary artery territory. Marked left ventricular hypertrophy was also found in the patient who died suddenly. No other cardiac abnormality was observed in either patient. These cases, together with those previously reported, suggest that myocardial bridging of the left anterior descending coronary artery can no longer be considered a benign coronary anomaly.

The value of the clinical history to assess prognosis of patients with ventricular tachycardia or ventricular fibrillation after myocardial infarction

Abstract: Multivariate analysis using 70 variables in 200 patients who suffered from ventricular tachycardia or ventricular fibrillation after myocardial infarction detected eleven variables that were associated with an increased risk of sudden arrhythmic death and cardiac death during a mean follow-up period of 2 years. Four of the II variables came from the patient's clinical history: (1) cardiac arrest at the time of the first spontaneous episode of arrhythmia, (2) New York Heart Association functional class for dyspnoea = III, (3) ventricular tachycardia or ventricular fibrillation occurring early (after 3 days and within 2 months) after myocardial infarction, (4) multiple myocardial infarctions before the first episode of ventricular tachyarrhythmia. Total mortality, incidence of sudden arrhythmic death and of non-sudden cardiac death increased with an increasing number (zero, one, two, three, four) of variables seen in individual patients. Patients with zero or one variable had an incidence of sudden death of 2·8% and a 4·2% incidence of non-sudden cardiac death at 26 months, while patients with more than two variables had a 13·5% and a 20·3% incidence respectively of sudden and non-sudden cardiac death. The strongest predictor of sudden death was the occurrence of cardiac arrest during the first spontaneous episode of ventricular arrhythmia. The strongest predictor of non-sudden cardiac death was the New York Heart Association functional class. The use of the four variables to stratify risk revealed seven subgroups of patients with incidences of sudden death ranging from 0 to 28%. Two questions from the clinical history revealed a subgroup of patients with a 0% incidence of sudden death at 26 months which constituted 40% of the total population (patients without cardiac arrest at the time of their first ventricular tachycardia which occurred >2 months after myocardial infarction). The same questions from the clinical history allowed the classification of patients into four different subgroups which showed incidences of cardiac death ranging from 4 to 42%. The clinical history allows accurate classification and risk stratification of patients with ventricular tachycardia or ventricular fibrillation after myocardial infarction. These data from the clinical history are necessary for interpretation of the results of antiarrhythmic treatment in these patients. They are also valuable in the interpretation of apparent beneficial or deleterious effects of new forms of antiarrhythmic treatment, because of the different prognosis of the different subgroups of patients presenting with ventricular tachyarrhythmias after myocardial infarction.

Characteristics, prognosis and treatment of the ventricular arrhythmias of right ventricular dysplasia.

Abstract: We studied 58 cases of arrhythmogenic right ventricular dysplasia (ARVD). Sustained monomorphic ventricular tachycardia (VT) was present in 50 patients, ventricular fibrillation (VF) in three (two also having VT), and non-sustained VT in the remaining seven. Different morphologies of VT were documented in 24 of the 50 patients with sustained VT. They had a left bundle branch block pattern in 96% of cases, without extreme deviation of the QRS axis, and a QRS relatively narrow and ample. These sustained VTs were triggered by provocative techniques. Holter recordings showed frequent ventricular extrasystoles in the great majority of cases. They were polymorphic in 78%, with runs of VT in 59% of patients. Spontaneous onset of VT occurred during exercise in 60% of cases, preceded by a sinus rate increase when recording was available. This is more frequent in angiographically localized forms of ARVD than in diffuse forms, and tends to disappear during follow-up. Only four cardiac deaths occurred after a follow-up of 8.8 +/- 7.2 years: three by acute heart failure, and only one by recurrent VF. Spontaneous disappearance of VT which became non-inducible was seen in four cases. Single antiarrhythmic drug therapy was judged satisfactory in 21 cases, and combined therapy in 19 other cases. Surgery of fulguration was performed in 17 cases, with 14 successes (nine of them with combined antiarrhythmic therapy). Despite a frequent lack of control of VT by antiarrhythmic drugs, the follow-up of ARVD seems good in patients with sustained VT. Some arguments favour the concept of a diffuse and progressive disease.

Vascular control by purines with emphasis on the coronary system

Abstract: There is growing evidence for several different roles for purines in the control of blood flow (1) Adenosine 5'-triphosphate (ATP) acts as a cotransmitter with noradrenaline and neuropeptide Y released from sympathetic perivascular nerves In most vessels it acts via P2x-purinoceptors to produce vasoconstriction synergistically with alpha-adrenoceptor activation, while in some coronary vessels it appears to act via P2Y-purinoceptors to produce vasodilatation in concert with beta-adrenoceptor activation (2) Adenosine, via P1-purinoceptors, acts as a prejunctional modulator of transmitter release from perivascular nerves; it also acts directly on vascular smooth muscle to produce vasodilatation (3) ATP is stored in and released from vascular endothelial cells (including those from the coronary bed) during changes in blood flow or during hypoxia, and acts via P2Y-purinoceptors on endothelial cells to release endothelium-derived relaxing factor, resulting in vasodilatation (4) ATP may be released together with substance P and calcitonin gene-related peptide from some sensory nerves during 'axon-reflex' activity when antidromic impulses pass down collaterals supplying blood vessels (5) Finally, there is evidence to suggest that ATP released from intrinsic (non-sympathetic) neurones in the airways and heart has potent actions on the resistance vessels

Experimental electrophysiology and arrhythmogenicity. Anisotropy and ventricular tachycardia

Abstract: In a 2-0 model of anisotropy, created by freezing the intramural and endocardia1 layers of a Langendorf perfused rabbit heart, sustained ventricular tachycardia (VT) with a cycle length of 130 ms andan excitable gap of 30 ms could be initiated by rapid pacing. High resolution mapping (256 points) of the thin surviving epicardial layer revealed that the VT was based on epicardial re-entry without the involvement of a gross anatomic obstacle and a central line of functional conduction block oriented parallel to the fibre. Microelectrode recordings from the centre of the ellipsoid circuit showed markedly prolonged action potentials, leading to 2:1 or 3:1 cellular responses. At the pivoting points prolonged action potentials with a 1:1 response were recorded. Immediately after termination of VT the same sites showed 1:1 responses with normal action potential duration. The various degrees of prolongation of the action potentials in the centre of functional anisotropic re-entry were caused by electrotonic current flow between the two limbs of the circuit, which were closely opposed but activated with a large time difference. Towards the pivoting points the phase difference between the two limbs of the circuit decreased, but because of slow transverse conduction around the pivoting points was still 30 ms. We conclude that the electrotonic prolongation of the action potentials at the pivoting points of anisotropic re-entry enlarges both the size and the cycle length of the circuit. Anisotropy thus contributes to the creation of stable VT with an excitable gap.

Symptoms and signs of heart failure in patients with myocardial infarction: reproducibility and relationship to chest X-ray, radionuclide ventriculography and right heart catheterization.

Abstract: 102 patients with myocardial infarction (MI) were examined by three clinicians, who independently recorded the following symptoms and signs: dyspnoea, a displaced apex beat, S3-gallop, rales, neck vein distension, hepatomegaly, and dependent oedema. Chest X-ray, radionuclide ventriculography, and (in 40 patients) right heart catheterization were carried out immediately after the physical examination. The clinicians frequently disagreed as to the presence of physical signs of heart failure in individuals. Moreover, these signs were of limited value in identifying patients with pulmonary vascular congestion on chest X-ray, reduced left or right radionuclide ventricular ejection fractions, enlarged ventricular volumes or haemodynamic evidence of ventricular dysfunction. We conclude that clinicians frequently disagree in the recognition of physical signs of heart failure, and that these signs have an unpredictable relationship to radiographic, radionuclide and haemodynamic measures of ventricular performance in patients with MI. Nevertheless, physical signs are useful in identifying patients with high risk of cardiac death.

Risk factors for acute myocardial infarction in Copenhagen. I: Hereditary, educational and socioeconomic factors

Abstract: The Copenhagen City Heart Study was designed to evaluate the incidence of and risk factors for cardiovascular disease. Information about potential risk factors was collected from 14 223 persons during an initial examination (1976–78) (attendance rate 74%). Information about new cases of acute myocardial infarction (AMI) was obtained from a second examination (1981–83), hospital registries and death registries up to December 31st 1983. This article deals with ‘basic’ risk factors, namely age, sex, some factors presumably of genetic character (family history of AMI, early parental death, height and earlobe crease) and social factors such as length of school education, income and marital status. The Cox regression model was used. As expected, the risk of first AMI increased with age and was highest among males. Earlobe crease and family history of AMI were found to be significant risk factors, the relative risk being 1.4 for both. No effect was found of early parental death and height. Low grade of education was associated with a higher risk, significantly so only in women, the relative risk being 1.7. Low income carried an increased risk, particularly for females. Cohabitation carried a higher risk, most pronounced in the low income group. Approximately half the effect of education was exerted through its influence on income and marital status.

Drug- and disease-induced changes of human cardiac beta 1- and beta 2-adrenoceptors.

Abstract: Cardiac beta-adrenoceptor density and subtype distribution has been determined in different kinds of heart failure. A decrease in cardiac beta-adrenoceptor function appears to be a general phenomenon in all kinds of heart failure. However, cardiac beta 1- and beta 2-adrenoceptors seem to be differentially affected in different kinds of heart failure: while in end-stage idiopathic dilated cardiomyopathy the diminished cardiac beta-adrenoceptor function is due to a selective loss in beta 1-adrenoceptors, in mitral valve disease, tetralogy of Fallot and end-stage ischaemic cardiomyopathy it is characterized by a concomitant reduction in beta 1- and beta 2-adrenoceptors. Chronic treatment of heart failure patients with beta-adrenoceptor antagonists leads to an up-regulation of cardiac beta-adrenoceptors, but in a subtype-selective fashion: beta 1-selective antagonists increase only cardiac beta 1-adrenoceptors, whereas non-selective antagonists increase both beta 1- and beta 2-adrenoceptors. Such a (subtype-selective) 'recovery' of cardiac beta-adrenoceptors may be one reason for the beneficial effects of low-dose beta-adrenoceptor antagonist treatment in patients with severe heart failure.

Long-term reduction in sudden deaths after a multifactorial intervention programme in patients with myocardial infarction: 10-year results of a controlled investigation

Abstract: SUMMARY Three-hundred and seventy-five unselected patients below 65 years of age and with acute myocardial infarction participated in a controlled investigation aimed at studying the effects of a multifactorial intervention programme on morbidity, mortality and risk factor control. After ten years' follow-up the significantly lower sudden death and coronary mortality observed three years after myocardial infarction still persisted in the intervention group (188 patients) compared with the control group (187 patients). The incidence of sudden death in the intervention group was 12.8% compared with 23.0% in the controls (P = 0.01). The incidence of coronary mortality was 35.1% and 47.1%, respectively (P = 0.02). No significant difference was found in the number of patients with clinical non-fatal reinfarctions (25.6% and 19.3%, respectively). During the first year, when the mortality difference was most marked, the use of beta blockers was not significantly different between the groups. The results suggest that with a multifactorial intervention programme which starts early after the infarction and lasts for years a significant long-term reduction in sudden deaths and coronary mortality can be attained.

High doses of L-carnitine in acute myocardial infarction: metabolic and antiarrhythmic effects

Abstract: Fatty acids accumulate in the muscle cells in some carnitine deficiency syndromes due to a variety of genetic defects in intermediary metabolism. L-Carnitine administration may relieve this excess by transporting acyl compounds out of the cell as acylcarnitine. Similar fatty acid accumulation occurs during myocardial ischaemia because of the decreased rate of beta-oxidation, and this has been put forward as a cause of ventricular arrhythmias. This study was carried out to investigate whether administration of high doses of i.v. L-carnitine in patients with acute myocardial infarction could increase urinary excretion of acylcarnitine and reduce early ventricular arrhythmias. Fifty-six patients suffering from acute myocardial infarction, admitted to the Coronary Unit between 3 and 12 h after the onset of symptoms, were included in the study. The design of the study was double blind, parallel and placebo controlled. Allocation of treatment to patients was done randomly after stratification (time from onset of pain and site of infarction). The first group (28 patients) received intravenous L-carnitine at a dose of 100 mg kg-1 b.w. every 12 h for 36 h while the second group (28 patients) received placebo intravenously. Immediately before starting treatment two blood samples were taken (at 5-min intervals) and a further 16 samples were taken at regular intervals over the following 48 h. Patients' urine was collected over the same period of time. Concentrations of free carnitine, short chain acylcarnitine esters and long chain acylcarnitine esters in serum and urine were measured.(ABSTRACT TRUNCATED AT 250 WORDS)

Beta-adrenoceptor regulation in the human heart: can it be monitored in circulating lymphocytes?

Abstract: In heart failure a decrease in cardiac beta-adrenoceptors presumably due to endogenous down-regulation by the elevated catecholamines is a general phenomenon Thus, attempts have been made to assess beta-adrenoceptor function in patients with chronic heart failure in order to monitor the functional state of cardiac beta-adrenoceptors The model most widely used is that of circulating lymphocytes that contain a homogeneous population of beta 2-adrenoceptors coupled to the adenylate cyclase/cyclic AMP system The biochemical and pharmacological properties of beta 2-adrenoceptors present in lymphocytes are quite comparable to those of beta 2-adrenoceptors in the human heart, but clearly different from those of human cardiac beta 1-adrenoceptors Furthermore, beta-adrenoceptor agonists and antagonists regulate lymphocyte beta 2- and cardiac beta 1- and beta 2-adrenoceptors in a subtype-selective fashion: while non-selective agonists (independent of exogenously applied or endogenously elevated) and antagonists affect both cardiac beta 1- and beta 2- as well as lymphocyte beta 2-adrenoceptors, beta 1-selective agonists and antagonists influence only cardiac beta 1-, but not cardiac and lymphocyte beta 2-adrenoceptors Finally, direct comparison of lymphocyte and cardiac beta-adrenoceptor densities revealed that changes in lymphocyte beta 2-adrenoceptors are significantly correlated with changes in cardiac beta 2-adrenoceptors, but not related to changes in cardiac beta 1-adrenoceptors Since beta 1-adrenoceptors predominate in all parts of the human heart, the use of lymphocyte beta 2-adrenoceptors as a tool for predicting the status of cardiac beta-adrenoceptors is, therefore, quite limited

Haemodynamic benefit of a rate-adapted A-V delay in dual chamber pacing.

Abstract: In dual chamber pacing, an improvement of exercise capacity is expected when the atrial refractory period is shortened, because the 2/1 point is increased. This objective can be achieved by greatly reducing atrioventricular delay (AVD) on exercise. Are such variations (up to 100-120 ms) detrimental from a haemodynamic standpoint? This study was performed to analyse this particular aspect of DDD pacing. Three DDD pacing modes, differing by their AVDs (fixed 200 ms AVD, fixed 150 ms AVD, and rate-adapted AVD) were tested in random order, with a haemodynamic protocol including ten patients with chronic atrio-ventricular (A-V) block. For the rate-adapted AVD pacing mode, AVD was reduced by 20 ms every 10 beats min-1 increment (from 220 ms at 90 beats min-1 to 100 ms at 150 beats min-1). Pacing rate was increased from 90 to 150 beats min-1 by increments of 10 beats min-1 every 5 min. Cardiac performance was significantly improved with the rate-adapted AVD above the two fixed AVDs, despite a large AVD variation. When AVD was rate adapted, cardiac index, stroke volume index and left ventricular systolic work index were generally higher and pulmonary capillary wedge pressure, pulmonary arterial pressure and systemic vascular resistances were generally lower, especially at 120, 130 and 140 beats min-1. Comparing the two fixed AVDs, 200 AVD improved cardiac function more at lower heart rates, whereas 150 AVD improved cardiac function more at higher heart rates. Despite its limitations, this study demonstrates that the potential benefits of reducing AVD with increasing heart rates should be twofold in dual chamber pacing: (a) haemodynamic, optimizing cardiac performance on exercise for all heart rates, especially in cases of organic heart disease; (b) electrophysiologic, permitting a sufficiently rapid maximal tracking rate in cases with long post-ventricular atrial refractory periods, allowing a satisfactory level of exercise.

Intermittent transdermal nitroglycerin monotherapy in stable exercise-induced angina: A comparison with a continuous schedule

Abstract: The aim of this study was to investigate nitrate tolerance during continuous treatment with nitroglycerin patches (NTG) as monotherapy, and to assess whether tolerance might be prevented by an overnight nitrate-free interval. Ten male patients, of mean age 53.2 years (range 41-62 years), with pathological coronary angiography and stable exercise-induced angina pectoris took part in a double-blind crossover study (two 15-day periods), during which the continuous and intermittent (12-h nitrate-free interval) application of NTG 20 mg (24 h)-1 patches were compared. Single-blind placebo was given acutely before and at the end of the crossover. Exercise testing was performed on a treadmill according to the Bruce protocol 4 and 12 h after dosing, both during placebo and at the end of the two active treatment periods. In comparison with continuous treatment, the intermittent administration of 20 mg (24 h)-1 NTG patches significantly increased ischaemic threshold and total work time at the 4th and the 12th hour. Night-time withdrawal of NTG transdermal delivery systems determined during the 15-day period a total of 11 night anginal attacks in six out of 10 patients (0.07 attacks per patient per nitrate-free interval).

Sex differences in cardiac adaptation to essential hypertension

Abstract: Left ventricular functional and structural adaptations to mild essential hypertension were assessed by 2D-guided M-mode echocardiography in a population of premenopausal and postmenopausal women (n = 29) who were matched with the same number of men with regard to mean arterial pressure, age and race. Premenopausal women had a thinner posterial wall (P less than 0.05), a smaller left ventricular systolic and diastolic diameter, and a smaller left ventricular mass than men with the same level of arterial pressure. Left ventricular performance indices, ejection fraction, velocity of circumferential fibre shortening, and the ratio of the end-systolic wall stress to the end-systolic volume index (a load-insensitive contractility index) were higher in women than in men. These sex differences were most pronounced before the menopause and tended to disappear thereafter. We conclude that in the presence of the same level of arterial pressure, women have smaller left ventricular dimensions and enhanced ventricular performance compared with men. These differences in cardiac adaptations between the genders may account for the lower risk of cardiovascular morbidity and mortality in premenopausal women with essential hypertension.