Showing papers in "European Heart Journal in 1991"

Validity of clinical diagnosis of heart failure in primary health care

Abstract: Validity of heart failure (HF) diagnosis was studied in 88 patients (37 men and 51 women), aged 45-74 (mean 61) years, in whom HF diagnosis had been newly made by primary health care physicians. Boston criteria for HF and a supplementary classification, based on information from clinical examinations and a 6-month follow-up, were used to define HF diagnosis as 'definite', 'possible' or 'unlikely'. Twenty-eight (32%) patients (21 men and seven women) had 'definite' HF and 46 (52%) (28 men and 18 women) had either 'definite' or 'possible' HF by both classifications. In 30 (34%) patients (six men and 24 women) HF diagnosis was 'unlikely' by both classifications. In conclusion, false-positive diagnosis of HF was common in primary health care, and HF diagnosis was more difficult in women than in men. Obesity, unrecognized symptomatic myocardial ischaemia without HF and pulmonary diseases were the most important conditions leading to false-positive HF diagnosis.

Standards for analysis of ventricular late potentials using high resolution or signal-averaged electrocardiography

Abstract: Sufficient data are available to recommend that the high-resolution or signal-averaged electrocardiogram can be used in patients recovering from myocardial infarction without bundle branch block to help to determine their risk for developing sustained ventricular tachyarrhythmias. However, no data are available regarding the extent to which pharmacologic or non-pharmacologic interventions in patients with late potentials have an impact on the incidence of sudden cardiac death. Therefore, controlled, prospective studies are required before this issue can be definitely answered. As refinements in techniques evolve, it is anticipated that the clinical value of high-resolution or signal-averaged electrocardiography will continue to increase in the future.

Affective disorders and survival after acute myocardial infarction. Results from the post-infarction late potential study.

Abstract: Psychological data from 560 male survivors of acute myocardial infarction (AMI) were documented in the third week after onset of AMI. The psychodiagnostic assessment was designed to detect different forms of depression as well as hyperactive behaviour. A complete follow-up of these patients, which covers a period of 6 months, is available. Our findings indicate that affective disorders play an important role in the post-acute phase after AMI although the extent of myocardial infarction (as defined by an ECG score) and behaviour responses are not significantly related to one another. Different subforms of depression are not influenced by a history of angina pectoris, the degree and location of myocardial infarction, the occurrence of late potentials and age, whereas dyspnoea ( P < 0·001) and the recurrence of myocardial infarction ( P < 0·001) favour depressive mood states. Twelve cardiac deaths and 17 arrhythmic events occurred during the study period; they were significantly predicted by severe forms of post-AMI depression as revealed by univariate analysis. The evidence was stronger for predicting cardiac death ( P < 0·001) than for arrhythmic events ( P = < 0·035). The effect remains of borderline significance for cardiac death if all risk factors with a significant univariate influence are included in a multiple logistic regression model. The effect of depression is illustrated by Kaplan—Meier survival curves separated for patient groups with high as compared to low degrees of depression. Hyperactivity showed no impact on patient survival.

Ventricular fibrillation in the Wolff-Parkinson-White syndrome.

Abstract: Ventricular fibrillation (VF) is a well-known but rare complication of the Wolff-Parkinson-White syndrome (WPW). Clinical and electrophysiological data of 23 patients with spontaneous VF were compared with data from 100 consecutive patients with WPW without VF but with symptomatic supraventricular tachycardia. The 23 patients were collected in a multicentre retrospective study in seven European centres. VF occurred in only one patient who was receiving antiarrhythmic drugs, and was the first manifestation of the syndrome in six. No significant differences were found between those with VF and without VF in age, complaints of palpitations, syncope, and presence of structural heart disease. The retrograde effective refractory period of the accessory pathway, the atrial refractory period and the fastest atrial pacing rate with 1:1 anterograde conduction over the accessory pathway were similar in both groups. Significant differences were found for sex, permanent pre-excitation on the electrocardiogram, type of documented supraventricular tachyarrhythmias, shortest RR interval less than or equal to 220 ms during spontaneous atrial fibrillation (AF), inducibility of supraventricular tachycardias, ventricular effective refractory period less than or equal to 190 ms, mean shortest RR interval during induced AF less than or equal to 180 ms and presence of multiple accessory pathways.(ABSTRACT TRUNCATED AT 250 WORDS)

The 'Sicilian Gambit' - A new approach to the classification of antiarrhythmic drugs based on their actions on arrhythmogenic mechanisms

Abstract: The Queen's Gambit is an opening move in chess that provides a variety of aggressive options to the player electing it. This report represents a similar gambit (the Sicilian Gambit) on the part of a group of basic and clinical investigators who met in Taormina, Sicily to consider the classification of antiarrhythmic drugs. Paramount to their considerations were 1) dissatisfaction with the options offered by existing classification systems for inspiring and directing research, development, and therapy, 2) the disarray in the field of antiarrhythmic drug development and testing in this post-Cardiac Arrhythmia Suppression Trial (CAST) era, and 3) the desire to provide an operational framework for consideration of antiarrhythmic drugs that will both encourage advancement and have the plasticity to grow as a result of the advances that occur. The multifaceted approach suggested is, like the title of the article, a gambit. It is an opening rather than a compendium and is intended to challenge thought and investigation rather than to resolve issues. The article incorporates first, a discussion of the shortcomings of the present system for drug classification; second, a review of the molecular targets on which drugs act (including channels and receptors); third, a consideration of the mechanisms responsible for arrhythmias, including the identification of "vulnerable parameter" that might be most accessible to drug effect; and finally, clinical considerations with respect to antiarrhythmic drugs. Information relating to the various levels of information is correlated across categories (i.e., clinical arrhythmias, cellular mechanisms, and molecular targets), and a "spread sheet" approach to antiarrhythmic action is presented that considers each drug as a unit, with similarities to and dissimilarities from other drugs being highlighted. A complete reference list for this work would require as many pages as the text itself. For this reason, referencing is selective and incomplete. It is designed, in fact, to provide sufficient background information to give the interested reader a starting frame of reference rather than to recognize the complete body of literature that is the basis for this article.

Reduction in QT dispersion by sotalol following myocardial infarction.

Abstract: Increased dispersion of ventricular recovery time is believed to be a substrate for serious ventricular arrhythmias. Class III antiarrhythmic drugs probably operate by decreasing dispersion through homogeneous prolongation of recovery time. A single surface QT value gives no information on recovery time dispersion but interlead variation in QT may be relevant. QTc dispersion was measured in 67 patients post myocardial infarction randomized to treatment with either sotalol or placebo. QTc dispersion was calculated as the difference between the maximum and minimum QTc in any surface electrocardiogram lead. Both maximum QTc and QTc dispersion varied considerably following infarction but throughout the 6-month follow-up period maximum QTc was significantly greater (P less than 0.05) and QTc dispersion significantly less (P less than 0.05) in patients on sotalol compared with placebo. These findings are in accord with expected changes in ventricular recovery time and provide strong support for the hypothesis that surface electrocardiogram QT variation reflects regional differences in ventricular recovery time.

Myocardial changes in pressure overload-induced left ventricular hypertrophy. A study on tissue composition, polyploidization and multinucleation.

Abstract: Morphological changes in human myocardium associated with pressure overload-induced left ventricular hypertrophy were studied in 22 normal and 21 hypertrophic hearts obtained at autopsy. Samples were obtained from the left lateral ventricular wall, half way between the apex and the base. Myocyte dimensions, polyploidization, multinucleation and relative volume fractions were studied. Regression analysis in relation to indexed heart weight yielded statistically significant correlation coefficients for myocyte volume: r = 0.69 (P less than 0.001), for degree of polyploidization: r = 0.77 (P less than 0.001), for number of nuclei per myocyte: r = 0.47 (P less than 0.01) and for volume fraction of myocytes: r = 0.32 (P less than 0.05). Approximate numbers of myocytes and connective tissue cells per left ventricle were calculated. Correlation coefficients related to indexed heart weight were r = 0.34 (P less than 0.05) for the number of myocytes and r = 0.76 (P less than 0.001) for the number of connective tissue cells. Based on regression analysis in relation to indexed heart weight, we calculated that a doubling of indexed heart weight was associated with an increase in mean myocyte volume by 65%, degree of polyploidization by 24%, multinucleation by 7%, number of myocytes by 20% and number of connective tissue cells by 141%. The volume percentage of myocytes decreased by 6% in favour of the connective tissue fraction. These changes in myocardial composition indicate that the term 'hypertrophy' inadequately describes the actual myocardial changes in response to pressure overload.

Doppler echocardiographic evaluation of pulmonary artery pressure in chronic obstructive pulmonary disease. A European multicentre study

Abstract: The feasibility, reproducibility and reliability of Doppler echocardiography in evaluation of pulmonary artery pressure in patients with chronic obstructive pulmonary disease (COPD) were determined in a multicentre study. In 100 COPD patients with mean pulmonary artery pressure ranging from 10 to 62 mmHg at cardiac catheterization, pulmonary pressure estimation was attempted by four Doppler echocardiographic methods. These methods comprised the calculation of transtricuspid and transpulmonary pressure gradients from Doppler-detected tricuspid or pulmonary regurgitation, the evaluation of right ventricular outflow tract velocity profiles with the measurement of right ventricular systolic time intervals and the measurement of the right ventricular isovolumic relaxation time. In 98 (98%) patients at least one of the methods could be employed. A tricuspid regurgitation jet was detected in 47 (47%) patients but its quality was adequate for measurement in 30 (30%). Pulmonary regurgitation jet velocity was measured only in five cases. The standard error of estimate in testing intra- and interobserver reproducibility of Doppler systolic time intervals was less than 5%. The predictive value of right ventricular outflow tract acceleration time less than 90 ms in the identification of patients with mean pulmonary artery pressure greater than 20 mmHg was 80%. Of Doppler echocardiographic data, best correlations with mean pulmonary artery pressure were found for the transtricupid gradient (r = 0.73, SEE = 7.4 mmHg), for the right ventricular acceleration time (r = 0.65, SEE = 8 mmHg) and right ventricular isovolumic relaxation time (r = 0.61, SEE = 8.5 mmHg).(ABSTRACT TRUNCATED AT 250 WORDS)

Tissue plasminogen activator and other risk factors as predictors of cardiovascular events in patients with severe angina pectoris.

Abstract: The value of measurements of the fibrinolytic factors, tissue plasminogen activator and plasminogen activator inhibitor, for predicting death and non-fatal cardiovascular events was studied in 213 consecutive patients with angiographically documented coronary artery disease. In the course of 4-year follow-up, 47 patients (22.1%) had at least one cardiovascular event. We found the incidence of cardiovascular events to be positively associated with high tissue plasminogen activator antigen concentration, in addition to previous myocardial infarction, low ejection fraction, hypertension, high body mass index and high triglyceride levels. Cholesterol was not found to be associated with cardiovascular events. A high concentration of tissue plasminogen activator antigen thus implies an increased risk of cardiovascular events in patients with severe angina pectoris.

Effect of acupuncture in patients with angina pectoris

Abstract: Twenty-one patients with stable effort angina pectoris were randomized in a crossover study to 4 weeks traditional Chinese acupuncture or placebo tablet treatment. The patients had at least five anginal attacks per week in spite of intensive treatment. Acupuncture was given three times per week at main points Neiguan (Pericardium 6), Tongli (Heart 5), Xinshu (Urinary Bladder 15), Pishu (Urinary Bladder 20) and Zusanli (Stomach 36). Previous antianginal treatment remained unchanged during the whole study. During the acupuncture period, the number of anginal attacks per week was reduced from 10.6 to 6.1 compared with placebo (P less than 0.01). Accordingly, the performance before onset of pain during exercise test increased from 82 W to 94 W (P less than 0.05). However, maximal performance did not increase after acupuncture. Intensity of pain at maximal workload decreased from 1.4 to 0.8 (scale 0-4, P less than 0.01). Further, ST-segment depressions at maximal comparable load decreased from 1.03 to 0.71 mm after acupuncture (P less than 0.01). A life quality questionnaire confirmed improved feeling of well-being. Thus, acupuncture showed an additional beneficial effect in patients with severe, intensively treated angina pectoris.

Natural history of severe mitral regurgitation.

Abstract: The aim of this retrospective study was to review the outcome of 216 patients (pts), investigated for severe mitral regurgitation (MR) between January 1980 and December 1987. Definition of 'severe' was mainly clinical: MR sufficiently advanced for the cardiologist to investigate whether surgery should be imminent. One hundred and sixty two pts (group 1) were operated on; 54 (group 2) did not undergo surgery. Baseline characteristics were similar in the two groups, except for aetiology (less dystrophic and more ischaemic MR in group 2), functional class (88.3% class III or IV in group 1 vs 48.1% in group 2; P = 0.001), pulmonary pressures (lower in group 2) and left ventricular ejection fraction (group 1: 0.66 +/- 0.13; group 2: 0.56 +/- 0.17; P = 0.001). Mean follow-up after hospital admission or surgery was comparable in the two groups (group 1: 3.9 +/- 2.5 years; group 2: 3.5 +/- 2.7 years). Three pts (group 2) were lost to follow-up. Sixty-three pts died; 35 of the 162 operated on; 28 of the 54 non-operated on. Actuarial survival rate at 8 years was 74.0 +/- 4.3% in group 1 vs 33.2 +/- 9.2% in group 2 (P = 0.001). These results confirm that the prognosis of severe MR is poor if it is not operated on, whereas the postoperative course of severe MR, when operated on in time, is good.

Progression of valvar aortic stenosis: a long-term retrospective study.

Abstract: Aortic valve stenosis is a potentially serious condition. Progression from mild to severe aortic stenosis is well-recognized but there are few data as to the likely rate of progression. Clinical outcome and cardiac catheterization data were reviewed for 65 patients with valvar aortic stenosis. Each patient had been investigated by cardiac catheterization on at least two occasions, the interval between studies ranging between 1 and 17 years (mean 7 years). In 60 cases the aortic valve gradient had increased, from a median of 10 mmHg (range 0-60) to a median of 52 mmHg (range 15-120). The mean rate of increase of gradient was 6.5 mmHg per year, and was significantly faster in patients in whom there was aortic valve calcification or aortic regurgitation present at the first catheter study (P less than 0.02). This study shows that progression of aortic stenosis may be very rapid, and correlates with valve calcification and regurgitation. If cardiac surgery is proposed for co-existing coronary or mitral valve disease in patients with mild or moderate aortic valve gradients, then aortic valve replacement should be considered at that time.

Catecholamine release and arrhythmias in acute myocardial ischaemia.

Abstract: Increased sympathetic activity is assumed to contribute substantially to the occurrence of malignant arrhythmias in patients with coronary heart disease, since the rate of sudden cardiac death is significantly reduced by β-adrenoceptor blockade, but not by antiarrhythmic agents such as flecainide or encainide. During acute myocardial ischaemia, adrenergic stimulation of the ischaemic myocardium is independent of plasma catecholamines. Rather, it is caused by the combination of excessively high local noradrenaline concentrations and an enhanced responsiveness of the myocyte to catecholamines. Myocardial ischaemia of 15min duration results in a 100-fold increase in catecholamine concentrations within the extracellular space of the ischaemic zone, a two-fold increase in functionally coupled α-adrenoceptors, and a 30% increase in β-adrenoccptors. Within the first l0min of ischaemia, the myocardium is protected from excessive catecholamine release. Ischaemia-associated metabolic alterations, such as extracellular potassium accumulation, acidosis, and especially the accumulation of adenosine reduce the transmitter release caused by central sympathetic activation. Furthermore, the functional neuronal amine reuptake (uptake,) prevents excessive local accumulation of noradrenaline. With progression of ischaemia to more than 10min, local nonexocytotic catecholamine release becomes predominant. This release is independent of central sympathetic nerve activity, availability of extracellular calcium, activation of both neuronal calcium channels and protein kinase C, and it is not accompanied by the release of sympathetic cotransmitters such as neuropeptide Y. It has been demonstrated to be nonexocytotic and to be caused by a carrier-mediated transport of noradrenaline from the sympathetic nerve ending into the synaptic cleft. This release is not modulated through presynaptic receptors. It is, however, suppressed by blockers of uptake, and by inhibitors of sodium-proton exchange. Depletion of cardiac catecholamine stores by chronic surgical or chemical sympathectomy effectively suppresses malignant arrhythmias induced by experimental coronary ligature. Accordingly, inhibitors of nonexocytotic noradrenaline release, such as uptake, blocking agents or sodium-proton exchange inhibitors, effectively reduce the occurrence of ischaemia-associated ventricular fibrillation, emphasizing the relevance of nonexocytotic release mechanisms in myocardial ischaemia.

Microalbuminuria is an early response following acute myocardial infarction.

Abstract: Ninety-six patients admitted to two coronary care units with suspected acute myocardial infarction were studied. The diagnosis was confirmed in 44, the remaining 52 were used as a control group. The first urine passed after admission, together with early morning urines on the following 3 days, were saved in all patients. Urinary albumin and IgG were measured by automated immunoturbidimetry and expressed as the protein creatinine ratio in mg.mmol−1. The log mean (SD) albumin creatinine ratios for the first urine passed in the myocardial infarction and non-myocardial infarction patient groups were 6.2(4.2) and 1.3(3.4) respectively. The difference in log mean albumin creatinine ratio was 4–9 mg.mmol−1, 95% CI3.4 to 6.2 mg.mmol−1 t=6.127 df=94, P<0.0001. The median IgG creatinine ratio for the first urine passed after admission in myocardial infarction patients was 1.0 mg.mmol−1 (95% Cl 0.5 to 1.2) and for non-myocardial infarction patients 0.3 (95% Cl 0.2 to 0.4). Increased urinary protein excretion appears to be an early and proportional response to acute myocardial infarction.

Autoantibodies against the β-adrenergic receptor in human myocarditis and dilated cardiomyopathy: β-adrenergic agonism without desensitization

Abstract: The serum of patients with myocarditis and dilated cardiomyopathy contains immunoglobulins capable of causing in vitro acceleration of beating of neonatal rat heart myocytes. This effect is stereoselectively inhibited by (-)-propranolol and is inhibited also by the beta 1-selective adrenergic antagonists, bisoprolol and metoprolol. This effect is not reversed by washing and continues unabated for at least 24 h.

Pathomorphological aspects, aetiology and natural history of acquired mitral valve stenosis

Abstract: Commissural fusion, leaflet thickening and alteration of the subvalvular apparatus are dominant mechanisms causing clinically important mitral stenosis (MS) of rheumatic origin. Calcification and a consequent decrease in leaflet mobility are subsequent features in rheumatic MS and may be the primary mechanisms in MS of degenerative origin. In 1051 consecutive patients with pure or predominant MS requiring surgical intervention, aetiology was rheumatic in 76.9%, infective in 3.3%, degenerative (severe annular and leaflet calcification) in 2.7% and congenital (Lutembacher syndrome) in 1.2%; it was the result of systemic lupus erythematosus (n = 4), carcinoid heart disease (n = 2), endomyocardial fibrosis (n = 2) and rheumatoid arthritis (n = 2) in less than 1%, while in 14.5% of these patients aetiology remained unclassified. The natural history of rheumatic MS is characterized by an asymptomatic latent period, following the initial rheumatic fever (RF). In a prospective study of MS (n = 159) the mean interval between RF and the appearance of symptoms was 16.3 +/- 5.2 years. Twenty-five years after the initial RF 8% of the patients were still asymptomatic, 9% were class II (NYHA), 33% class III and 50% had been operated or were class IV. Progress from mild to severe disability took 9.2 +/- 4.3 years on average. When valve surgery was indicated but refused by the patients, survival with medical treatment was 0.44 +/- 0.06 after 5 years, 0.32 +/- 0.08 after 10 years and 0.19 +/- 0.09 after 15 years.(ABSTRACT TRUNCATED AT 250 WORDS)

The incidence of malignant vasovagal syndrome in patients with recurrent syncope

Abstract: We reviewed 322 patients with recurrent syncope between 1984 and 1988. Investigation included limited intracardiac electrophysiological study in all cases with programmed extra-stimulus studies in 48 cases. In 93 patients (29%), all investigations were normal, (including negative extrastimulus in 30). In the other 229 cases syncope was explained by AV-block (n = 111, 34%), sinus node disease (n = 68, 21%), carotid sinus syndrome (n = 32, 10%) and inducible sustained tachyarrhythmia (n = 18, 6%). Prolonged 60 degrees head-up tilt was performed in 71 out of 93 patients with unexplained syncope, and reproduced vasovagal syncope and presenting symptoms in 53 (75%), or 16% of the whole population reported. These patients were diagnosed as having malignant vasovagal syndrome. Positive tilts were significantly less common in a group of 27 subjects of similar age without a history of syncope (7%), and a random sample of 37 patients with atrioventricular block (n = 16), sick sinus syndrome (n = 18) and inducible tachyarrhythmia (n = 3), (19%, 11% and 0% respectively, P less than 0.01). From this retrospective review it appears, therefore, that tilt testing is a valuable provocative tool for vasovagal syncope and may reduce the number of syncopal patients that remain undiagnosed, although these early observations do not allow an exact appraisal of the sensitivity and specificity of the tilt test.

Heart rate variability in left ventricular hypertrophy and heart failure, and the effects of beta-blockade : a non-spectral analysis of heart rate variability in the frequency domain and in the time domain

Abstract: An analysis of heart rate (HR) variability (HRV) was based on quantifying the number and amplitude of HR fluctuations over long (8–30 cycles) and short (2–4 cycles) sequences of acceleration and deceleration-forming oscillations. The ‘product’ (number times amplitude) is an equivalent of the power spectrum in the frequency domain. In the time domain, positive correlations with HR were found for the number of long (L) sympathetic-mediated oscillations, whereas they were negative for short (S) vagally-mediated oscillations. The L/S ratio, an index of the autonomic nervous system (ANS) balance, closely paralleled the circadian HR values. HRV was studied in the ambulatory ECG of three groups of 15 normal adults (group I), 13 patients with left ventricular hypertrophy (LVH, group II) and 13 patients-with heart failure (HF, group III). In basic conditions the mean HR was 77.1 ±l.9 beats min−1 (mean±SEM) in group 1, 76.8±3.3 in II, 79.5±3.5 in III (P = NS). The different types of oscillations had smaller 24-h average values of the product in groups II and III than in group I, but the trends did not reach significance. However, the pooled 24 hourly values of the L/S ratio in group I (1.17 ± 0.09) were lower than in group II (1.33 ±0.06, P<0.05 at Ancova) and higher than in group III (1.06 ±0.09, P<0.001). A 3-day treatment with acebutolol non-uniformly slowed the mean HR: -9.5% in group I, -18.1% in II and -19.1% in III (P<0.001), and uniformly diminished the L/S ratio by 17% to 20% (P<0.01). In conclusion, the sympathetic predominance of the ANS balance in LVH and HF is reflected by the beta-blockade induced HR decrease that is twice as marked in patients as in controls. In basic conditions HRV tends to be depressed in LVH and even more in HF. The ANS imbalance, however, has different modalities depending on the presence of HF, probably because of the different status of beta-adrenergic receptors in this condition.

An in vivo validation of quantitative blood flow imaging in arteries and veins using magnetic resonance phase-shift techniques

Abstract: Magnetic resonance (MR) techniques have recently been introduced, allowing quantitative measurement of blood flow with high spatial and temporal resolutions. These techniques are based on the phase of the MR signal rather than on the amplitude, and are referred to as MR phase or velocity mapping. Clinical validation is still lacking. We therefore performed an in vivo validation of such a technique in 17 healthy volunteers. Velocity maps were acquired at 50 ms intervals over the cardiac cycle in the aorta, superior and inferior vena cava. Plots were made of flow velocity and volume flow vs time and used for calculation of left ventricular stroke volume (SV), cardiac output (CO) and venous return. Comparison with Doppler ultrasound (x) yielded y=−7.5+1.1x (r = 0.76) for SV measurements (ml), and y = 0.3 + 0.9x (r=0.86) for CO calculations (I min− 1). Comparison between MR SV (x) and MR determination of venous return (y), obtained by summation of the flow volumes per cardiac cycle in the superior and inferior vena cava, was close to identity, y= 1.3 +1.0 (r = 0.91). Also, preliminary applications are presented in patients with aortic diseases. The findings of this study show that magnetic resonance velocity imaging can be accurately applied in vivo as a non-invasive means of measuring flow.

Ventricular conduction defects and atrial fibrillation after coronary artery bypass grafting. Multivariate analysis of preoperative, intraoperative and postoperative variables

Abstract: Preoperative, intraoperative and postoperative variables, which might play a role in the development of ventricular conduction defects (VCD) and atrial fibrillation (AF) following coronary artery bypass grafting (CABG), were evaluated in 236 consecutive patients. VCD and AF developed postoperatively in 15·5% of patients. 4·5% had VCD (subgroup A), 11·0% had AF (subgroup B). In 84·5 of patients VCD and AF did not occur (subgroup C). Univariate analysis showed statistically significant differenes between subgroups A and C with respect to.. left main sign stenoses and number of diseased vessels. Bypass pump time and aortic cross-clamp time were significantly longer in subgroup B. Multivariate analysis showed a significantly greater incidence of left main disease and of right coronary artery occlusion associated with significant stenosis of the proximal left anterior descending artery in subgroup A. In subgroup B, the duration of aortic cross-clamp time was signficantly higher. Ischaemic injury, with increasing duration of cardioplegic arrest, seems to play a key role in the development of AF. Nonhomogeneous cardioplegic delivery to critical areas of myocardium, and particularly to the specialized conducting system, may cause VCD after CABG.

Molecular probes for detection of persisting enterovirus infection of human heart and their prognostic value

Abstract: Enteroviruses are well recognized in the aetiology of myocarditis. Molecular hybridization using enterovirus group-specific probes shows that virus can be detected in endomyocardial biopsies and persists in myocardium after the inflammation heals. Virus persistence is associated with the subsequent development of dilated cardiomyopathy, progressing to end-stage disease requiring cardiac transplantation. Infectious virus cannot usually be isolated from myocardium nor can virus-specific antigens be detected after the initial inflammatory stage. Patients with healed myocarditis or dilated cardiomyopathy may have no histological evidence of inflammation despite detection of virus-specific RNA sequences by molecular hybridization. Persisting enterovirus RNA in dilated cardiomyopathy is the strongest known predictor of poor prognosis. The molecular mechanism of virus persistence is the selection of defective virus mutants during the initial phase of disease.

Hypercoagulable state and thromboembolism following warfarin withdrawal in post-myocardial-infarction patients.

Abstract: Nine out of 47 (19%) patients on chronic anticoagulation with warfarin, as secondary prophylaxis after myocardial infarction, initially treated with streptokinase, had thromboembolic complications within 4 weeks after sudden (7/25) or gradual (2/22:NS) warfarin withdrawal. The biochemical effects of warfarin withdrawal were repeatedly studied in 20 of the patients during the first 14 days following drug cessation. During the first 4 days, the levels of coagulation factors VII and IX increased more rapidly than proteins C and S. Thus, a gap was created between the factors provoking and inhibiting the coagulation process. Furthermore, plasma concentrations of fibrinopeptide A (FPA) increased, reflecting activation of the coagulation system. These laboratory findings suggest that withdrawal of warfarin creates a transient hypercoagulable state, imposing a risk of thromboembolic events in patients given anticoagulant treatment as secondary prophylaxis following myocardial infarction.

Beta-adrenoceptor antibodies and genetics in dilated cardiomyopathy--an overview and review.

Abstract: Autoantibodies against the cardiac beta-adrenoceptor are present in 30-40% of patients with idiopathic dilated cardiomyopathy and can be detected using ligand binding inhibition, immunoprecipitation or immunoblotting. The functional consequences of the antibody-receptor interactions are two-fold: (a) in isolated cardiac myocytes, diluted sera from cardiomyopathy patients induce internalization of the beta-receptors which are subsequently degraded intracellularly; (b) in membrane preparations, anti-receptor antibodies inhibit selectively the activity of isoproterenol-sensitive adenylate cyclase. The presence of anti-receptor antibodies is strongly linked to the HLA-DR4 phenotype: 72% of the HLA-DR4 patients in our series had anti-beta-receptor antibodies compared with 22% of the HLA-DR4-negative patients (most of which typed as HLA-DR1). Conversely, 67% of the antibody-positive patients typed as HLA-DR4, compared with only 10% of the antibody-negative patients. These results indicate the presence, in a subset of cardiomyopathy patients, of immunogenetical factors which may modulate myocardial beta-adrenoceptor function.

Endothelium-derived nitric oxide: the endogenous nitrovasodilator in the human cardiovascular system.

Abstract: The L-arginine pathway within endothelial cells in the blood vessel wall is the source of production of the endogenous nitrovasodilator, nitric oxide (NO). NO is released under basal conditions and in response to various stimuli such as shear stress and in response to platelet-derived products, coagulation factors and hormones. NO is the mediator of endothelium-dependent relaxation in the circulation and exerts its effects by activating soluble guanylyl cyclase in vascular smooth muscle, which in turn leads to the formation of cyclic guanosine monophosphate (cGMP) and to relaxation. In addition to its effects on vascular smooth muscle, NO is also released abluminally to interact with circulating platelets. Increases in cGMP in platelets are associated with a decreased adhesion and aggregation of cells. Thus, endothelium-derived NO, through its vasodilator and anti-aggregatory properties, prevents vasospasm and thrombus formation in the circulation and thereby helps to maintain blood flow to vital organs such as the heart. Therapeutic nitrates also exert their effects by releasing NO from their molecules and activating soluble guanylyl cyclase. Their effects are particularly pronounced in arteries without endothelium and are reduced in the presence of the basal formation of endothelium-derived NO in intact arteries. The lower basal formation of endothelium-derived NO in veins, as compared to arteries, contributes to the greater sensitivity of venous circulation to nitrates. Thus, the endothelial L-arginine pathway plays an important protective role in the local regulation of blood flow and through its vasodilator and antiplatelet properties.

Effects of quinapril on exercise tolerance in patients with mild to moderate heart failure.

Abstract: The objective of this double-blind, placebo-controlled, randomized multicentre study was to determine whether treatment with the new non-sulfhydryl angiotensin converting enzyme (ACE) inhibitor quinapril, as an addition to maintenance therapy with digitalis and/or diuretics, would improve exercise tolerance and patients' symptomatology over a treatment period of 3 months. Two hundred and twenty-five patients with mild to moderate heart failure were studied in four parallel treatment groups receiving either placebo or quinapril in a dose of 10, 20, or 40 mg day-1. Compared to placebo, quinapril therapy resulted in a significant improvement in exercise time. The improvement in exercise tolerance was dose-related and showed a significant increase at the end of the study in the patients who completed the trial and in an intent-to-treat analysis. Twenty-six patients were on monotherapy with quinapril without concomitant medication. In this subgroup of patients, the increase in exercise time was comparable to the subgroup of patients on diuretic treatment alone. After the 12-week study, 189 patients entered an open-label trial for 12 months, in which the dose of the ACE inhibitor could be adjusted according to clinical response. Despite a reduction in the daily dose of quinapril, the patients reached the same level of exercise capacity as in the 3-month study. No serious side effects were recorded, particularly no symptomatic hypotension or deterioration of renal function. The results of the study show that quinapril has a significant favourable effect on exercise tolerance and symptoms in patients with mild to moderate heart failure.

Coronary reserve in patients with aortic valve disease before and after successful aortic valve replacement

Abstract: In patients with aortic valve disease and normal coronary angiograms coronary reserve was determined by the coronary sinus thermodilution technique. Three groups of patients were studied: 37 preoperative patients; 18 different patients 12-52 months after aortic valve replacement and seven control subjects with no cardiac disease. Coronary flow ratio (dipyridamole/rest) was diminished in preoperative compared with postoperative patients (1.66 +/- 0.44 vs 2.22 +/- 0.85; P less than 0.05) as well as with controls (2.80 +/- 0.84; P less than 0.01), and corresponding coronary resistance ratio (dipyridamole/rest) was higher in preoperative patients than in both other groups (0.61 +/- 0.17 vs 0.48 +/- 0.14; P less than 0.05 vs 0.37 +/- 0.10; P less than 0.01). Differences in the flow ratio, but not in the resistance ratio, were significant (P less than 0.05) in patients after aortic valve replacement compared with controls. Total coronary sinus blood flow at rest was elevated in preoperative compared with both postoperative patients and controls (252 +/- 99 vs 169 +/- 63; P less than 0.01; vs 170 +/- 35 ml.min-1, P less than 0.05), whereas flows after maximal vasodilation did not differ among the three groups (416 +/- 184 vs 361 +/- 150 vs 488 +/- 235 ml.min-1). Postoperative patients showed a distinct, though not total regression of left ventricular angiographic muscle mass index and wall thickness. Nine of the 18 postoperative patients showed a normal coronary flow reserve and nine showed subnormal response. These two subgroups did not differ with respect to preoperative macroscopic and microscopic measures of hypertrophy. Thus in aortic valve disease, the reduced coronary vasodilator capacity is mainly due to an elevated coronary flow at rest, while the maximal coronary blood flow achieved is identical to that of postoperative patients and controls. With regression of left ventricular hypertrophy, flow at rest decreases and this leads to a distinct improvement of coronary flow reserve.

Cardiac alterations in 36 consecutive patients with idiopathic haemochromatosis: polygraphic and echocardiographic evaluation

Abstract: Thirty-six consecutive patients with idiopathic haemochromatosis (IH) were studied by electrocardiography (ECG), polygraphy, M-mode and 2-D echocardiography and Doppler-echocardiography. No significant correlations were found between ECG, PEP/LVET ratio and echocardiographic measurements. Left ventricular (LV) enlargement with impaired LV systolic function was present only in three patients (5.5%), of whom two died during iron-depleting therapy because of cardiovascular complications. Compared with controls, echocardiographic abnormalities were significantly more frequent and marked in subjects with higher iron overload than in those in whom it was lower. Ten patients were studied before and after iron depletion, nine of whom had only mild echocardiographic abnormalities at baseline examination. Significant reduction of end-diastolic thickness of the interventricular septum and LV mass (P less than 0.01 and less than 0.02 respectively) was observed. Also the end-diastolic thickness of the LV posterior wall and the end-systolic diameter of the left atrium reduced although not to a significant degree. The increased thickness of ventricular walls without impairment of LV systolic function is probably the first and still reversible cardiac alteration due to iron deposition in the myocardium. Later, with increasing iron overload, LV function becomes impaired and dilated cardiomyopathy develops. Early diagnosis and treatment of IH cardiopathy is needed before irreversible cardiac damage occurs.

Immune response to the endothelium in myocarditis, dilated cardiomyopathy and rejection after heart transplantation

Abstract: The role of endothelial cells in inflammatory heart disease and rejection after heart transplantation is only partly understood. To determine whether an immune reaction against endothelial cells occurs we examined endomyocardial biopsies from patients with myocarditis (n = 13), dilated cardiomyopathy (n = 23), no clinical rejection (n = 10) and moderate to severe rejection after heart transplantation (n = 10). These were compared to ‘normal’ donor hearts with monoclonal endothelial-specific antibodies EN4, Pal-E and F VIII-related antigen. Nearly all endothelial cells were stained positively with EN4. There were no significant changes in the binding of the antibodies except in rejection when Pal-E and F VIII-related antigen were significantly increased. It is concluded that apart from their possible role as antigen-presenting cells, endothelial cells are important targets in rejection after heart transplantation. Damage or cytolysis of endothelial cells may cause both altered transendothelial permeability and functional decrease in antigen presentation.

Alpha1adrenergic system and arrhythmias in ischaemic heart disease

Abstract: Several lines of experimental evidence obtained over the last decade indicate that alterations in the alpha 1-adrenergic receptor system may contribute significantly to arrhythmogenesis in the ischaemic heart. Under normal physiological conditions, alpha 1-adrenergic stimulation of myocytes elicits a modest increase in inotropy, a lengthening of repolarization secondary to a decrease in IK through activation of protein kinase C, and a decrease in automaticity in Purkinje cells due to an increase in Na+/K+ ATPase activity. These findings suggest that alpha 1-adrenergic stimulation of the myocardium would elicit an antiarrhythmic effect. However, during both early ischaemia and reperfusion there is an enhanced responsivity to alpha-adrenergic stimulation and a potent antiarrhythmic effect of alpha 1-adrenergic blockade in several species including the conscious dog. This enhanced alpha-adrenergic responsivity may be due to an increase in alpha 1-adrenergic receptors in ischaemic myocardium originating from a site distinct from the intracellular site for trafficking of beta-adrenergic receptors, possibly within or near the sarcolemma. Recently, we developed an isolated adult canine ventricular myocyte preparation which also exhibits a 2- to 3-fold reversible increase in alpha 1-adrenergic receptors in response to severe hypoxia (PO2 = less than 15 mmHg) associated with marked sarcolemmal accumulation of long-chain acylcarnitines (LCA) secondary to hypoxia-induced inhibition of beta-oxidation of fatty acids. The increase in alpha 1-adrenergic receptors is prevented by inhibition of carnitine acyltransferase I which precludes accumulation of LCA. The sarcolemmal accumulation of LCA increases membrane fluidity, suggesting that the alpha 1-adrenergic receptor may be latent within or near the sarcolemma and becomes accessible to a surface ligand only as membrane fluidity is altered. This conclusion is also supported by our findings that hypoxia elicits a marked increase in the coupling of the alpha 1-adrenergic receptor to inositol 1,4,5-trisphosphate (IP3) production in canine myocytes exposed to norepinephrine. IP3 has been shown to mobilize Ca2+ from the sarcoplasmic reticulum, thereby modulating the levels of intracellular Ca2+. Stimulation of hypoxic myocytes with norepinephrine also results in the appearance of delayed after-depolarizations and triggered rhythms, probably in response to an increase in intracellular Ca2+. In conclusion, these findings indicate that the alpha 1-adrenergic system can contribute to arrhythmogenesis in the ischaemic heart and that approaches to reduce the incidence of sudden cardiac death should include blockade of alpha 1-adrenergic receptors.