Showing papers in "European Heart Journal in 1990"
TL;DR: It is indicated that aortic distensibility in patients with coronary artery disease can be obtained non-invasively with a high degree of accuracy.
Abstract: Distensibility of the ascending aorta, measured non-invasively, was compared with values obtained by invasive techniques in 46 males (30 patients with coronary artery disease and 16 age-matched normal subjects). Aortic diameters were measured at a level 3 cm above the aortic valve using both echocardiographic and angiographic techniques. Aortic distensibility was calculated from the aortic diameters and aortic pressure or brachial artery pressure using the formula: 2 × (change in aortic diameter) /(diastolic aortic diameter) × (change in aortic pressure). Distensibility of the ascending aorta determined non-invasively was closely related to that obtained by direct measurements (r = 0.949, P<0.001). Patients with coronary artery disease had similar pressures, but markedly lower distensibility than normal subjects, as shown by both invasive and non-invasive techniques. The results indicate that aortic distensibility in patients with coronary artery disease can be obtained non-invasively with a high degree of accuracy.
436 citations
TL;DR: When atherosclerotic lesions of any type were present in coronary arteries, the amount of lipid and accompanying cell reactions were greatest in eccentric Thickening; intermediate lesions and atheroma were present only in eccentric thickening while fibroatheroma often extended beyond eccentric thickens.
Abstract: We have studied the cell and matrix composition of normal intima and of atherosclerotic lesions in the coronary arteries of 691 subjects less than 40 years old. These arteries were obtained at autopsy and fixed by perfusion with glutaraldehyde under physiological pressure. A defined segment of the left coronary artery, known for its susceptibility to develop advanced lesions, was studied by light and electron microscopy. The initial intimal lesion occurred in infants and consisted in an increase in intimal macrophages and presence of isolated lipid-laden macrophages (foam cells). At puberty, more substantial accumulations of foam cells, accompanied now by lipid droplets in smooth muscle cells and by thinly scattered extracellular lipid (fatty streaks), were present. After puberty, an increasing number of subjects had intermediate lesions and atheroma. Intermediate lesions, characterized by greatly increased extracellular lipid, were the link between fatty streaks and atheroma. Atheroma was characterized by a massive core of extracellular lipid that damaged arterial structure by displacing normal intimal cells and matrix. In the third and more often in the fourth decade, some atheroma contained greatly increased collagen and smooth muscle cells above the lipid core (fibroatheroma). Collagenization and thickening were more marked when evidence of thrombotic deposits was present on the surface or within lesions. Smooth muscle cells were present in the intima of all subjects from birth. In early lesions, lipid in the intima was not associated with an increase in the number of smooth muscle cells. Smooth muscle cells were increased in lesions containing massive extracellular lipid, more so in those having, in addition, a thrombotic component; smooth muscle cells with massive basement membranes occurred in advanced lesions. Macrophages and macrophage foam cells were the cells that increased intimal cellularity at the onset of lesions. Other cell types associated with lesions were lymphocytes, mast cells, and plasma cells, but all of these were less numerous than either smooth muscle cells or macrophages. From birth, intima was always thicker opposite the flow divider wall of a bifurcation (eccentric thickening). When atherosclerotic lesions of any type were present in coronary arteries, the amount of lipid and accompanying cell reactions were greatest in eccentric thickening; intermediate lesions and atheroma were present only in eccentric thickening while fibroatheroma often extended beyond eccentric thickening.
421 citations
TL;DR: Three methods for reconstructing the Frank VCG from the standard 12-lead ECG were studied and it was found that estimation of similarity by a distance measure could not replace diagnostic evaluation by skilled observers.
Abstract: Three methods for reconstructing the Frank VCG from the standard 12-lead ECG were studied. The first was based on multivariate regression, the second on a model of the cardio-electrical activity, and the third method used a quasi-orthogonal set of ECG leads. The methods were evaluated on a test set of 90 cases by a numerical distance measure and by the agreement in diagnostic classification of the original and reconstructed VCGs. The original and reconstructed VCGs were presented separately and in random order to three referees. Eighteen of the original VCGs were presented three times to estimate the intra-observer agreement. Kappa statistics were used to quantify the agreement between diagnostic classifications. Separately, one referee was simultaneously presented the original VCG and its three reconstructions for all cases. Each reconstruction VCG was classified as either diagnostically 'same' as the original, 'borderline' or 'different'. The performance of the regression method and the model-based method was comparable. Both methods were preferable to the quasi-orthogonal method. The kappa values for the preferred methods indicated a good to excellent diagnostic agreement between the original and reconstructed VCGs. Only one out of ninety VCGs that were reconstructed with the regression method was classified as 'different' compared with the original VCGs; three VCGs were classified as 'different' with the model-based method. It was also found that estimation of similarity by a distance measure could not replace diagnostic evaluation by skilled observers.
326 citations
TL;DR: Nitroglycerin reduces left ventricular afterload through arterial dilation as well as preload through venous dilation, which effect on afterload is not apparent from measurement of pressure in the brachial artery.
Abstract: Nitroglycerin (0-3 mg) was administeredsublingually to 14patients undergoing cardiac catheterization, and pressure waves compared in the ascending aorta and brachial artery. After nitroglycerin, ascending aortic systolic pressure fell in all cases (by 6–44, average 22 mmHg) whereas brachial systolic pressure remained unchanged (in three) or fell to a lesser degree (4–33, average12 mmHg). Diastolic pressure did not change significantly. Alterations in pressure and in wave contour were explained on the basis of arterial dilation, with reduction in wave reflection. Nitroglycerin reduces left ventricular afterload through arterial dilation as well as preload through venous dilation. This effect on afterload is not apparent from measurement of pressure in the brachial artery.
304 citations
TL;DR: Data suggest a beneficial effect, but a definitive answer regarding the benefit of beta-blockade in diabetic patients after acute myocardial infarction would require a prospective, randomized study.
Abstract: Whether diabetic patients may benefit, compared with non-diabetic patients, from beta-blocker therapy following acute myocardial infarction was examined in a large multicentre cohort of 2024 patients, including 340 diabetics, 281 of whom survived hospitalization. One-year mortality following discharge was 17% for diabetics compared with 10% for non-diabetics (P less than 0.001). However, diabetics discharged on beta-blockers had a 1-year mortality of only 10%, compared with 23% for diabetics not on beta-blockers. In non-diabetics, mortality rates were 7% and 13% for those taking and not taking beta-blockers, respectively. Bias in patient selection for beta-blocker therapy might be responsible for the trends exhibited in our population since patients were not randomized to treatment. In diabetics, evidence of pulmonary congestion on X-ray was more prevalent than in non-diabetics; this appeared to be true both for patients taking beta-blockers and for those not taking beta-blockers. However, even in diabetics without evidence of pulmonary congestion on X-ray, 1-year mortality was 7% vs 17% for those with and without beta-blocker therapy, respectively (P less than 0.04). In multivariate analysis, beta-blocker use was an independent predictor of 1-year cardiac survival following hospital discharge for all diabetics, even those without evidence for pulmonary congestion on X-ray, but not for non-diabetics. These data suggest a beneficial effect, but a definitive answer regarding the benefit of beta-blockade in diabetic patients after acute myocardial infarction would require a prospective, randomized study.
227 citations
TL;DR: It is concluded that the corrected pulse contour method estimates cardiac output accurately, even when heart rate, blood pressure, and total peripheral resistance change substantially.
Abstract: Most pulse contour methods are unreliable under changing haemodynamic conditions, because no corrections are made for pressure-dependent compliance and reflections of pressure waves. The pulse contour method of Wesseling includes such corrections. Four thermodilution measurements equally spread over the ventilatory cycle were used to calibrate and evaluate this pulse contour method. We designed a prototype incorporating a combination of the thermodilution method and pulse contour method and evaluated its potential for monitoring patients undergoing coronary bypass graft operation. Eight to 12 times during the operation, cardiac output was estimated by pulse contour and by thermodilution. The results were compared: the linear regression between the methods was COpc=O.3+O.94 . COth'(r=O.94). The standard deviation for the difference between the methods against the mean of the methods was 10.6%. We concluded that the corrected pulse contour method estimates cardiac output accurately, even when heart rate, blood pressure, and total peripheral resistance change substantially.
179 citations
TL;DR: Overall cardiovascular function at rest in most healthy elderly individuals is adequate to meet the body's need for pressure and flow, and some elderly individuals exhibit cardiac dilatation which produces an increased stroke volume sufficient to counter the well-known age-related decrease in exercise heart rate, such that high levels of cardiac output can be maintained during exercise.
Abstract: Overall cardiovascular function at rest in most healthy elderly individuals is adequate to meet the body's need for pressure and flow. The resting heart rate is unchanged. Heart size is essentially not different in younger vs older adults, but heart wall thickness increases modestly, due largely to an increase in myocyte size. While the early diastolic filling rate is reduced, an enhanced atrial contribution to ventricular filling in elderly individuals maintains filling volume at a normal level. Although systolic pressure at rest increases with age, the resting end-systolic volume and election fraction are not altered, due partly to the increase in left ventricular thickness. Physical work capacity declines with advancing age, but the extent to which this can be attributed to a decrement in cardiac reserve is not certain. Part of the age-related decline in maximum oxygen consumption appears to be due to peripheral rather than central circulatory factors, e.g. to a decrease in muscle mass with age during exercise, the ability to direct blood flow to muscles, and the ability of muscle to utilize oxygen. Some elderly individuals exhibit cardiac dilatation which produces an increased stroke volume sufficient to counter the well-known age-related decrease in exercise heart rate, such that high levels of cardiac output can be maintained during exercise. Still, in these individuals, the exercise-induced reduction in end-systolic volume and increase in ejection fraction is less than in younger individuals. A similar haemodynamic profile occurs in individuals of any age who exercise in the presence of beta-adrenergic blockade.(ABSTRACT TRUNCATED AT 250 WORDS)
152 citations
TL;DR: A 6-month double-blind placebo-controlled study to examine the benefit of adding 60 mg of TMZ vs placebo to the classical therapy, excluding those previously treated with calcium-antagonists, conversion enzyme inhibitors, vasodilators and antiplatelet agents.
Abstract: Trimetazidine (TMZ) has been shown to have anti-ischaemic properties improving exercise tolerance without haemodynamic effects. A 6-month double-blind placebo-controlled study was carried out in 20 patients, mean age 59 +/- 6 years, to examine the benefit of adding 60 mg of TMZ vs placebo to the classical therapy, excluding those previously treated with calcium-antagonists, conversion enzyme inhibitors, vasodilators and antiplatelet agents. All patients had severe ischaemic cardiomyopathy, confirmed by coronary angiography; six were in NYHA class IV; 14 in NYHA class III; four had mild recurrent angina pectoris. assessment included clinical and biological evaluation, electrocardiography (ECG), 24-h ECG monitoring, cardiac volume evaluation with chest X-ray, left ventricular fractional shortening by echocardiography, left ventricular ejection fraction by radionuclide angiography. Baseline characteristics were similar in placebo (11 patients) and TMZ (nine patients) groups. Eighteen patients (nine in each group) were followed up for 6 months. In eight patients of the placebo group, treatment had to be modified (addition of calcium antagonists: four patients, conversion enzyme inhibitors: two patients; digitalics: one patient; diuretics: one patient). In the TMZ group, digitalic therapy was withdrawn in one patient and added in one patient (P less than 0.01). At 6 months, all TMZ group patients were free from angina; dyspnoea was improved in all TMZ patients and in only one placebo patient (P less than 0.001). Ejection fraction, increased by 9.3% in the TMZ group and decreased by 15.6% in the placebo group (P less than 0.018), CV decreased by 7% with TMZ, increased by 4% with placebo. (P = 0.034).(ABSTRACT TRUNCATED AT 250 WORDS)
124 citations
TL;DR: Overall survival was good in this population of all stage dilated cardiomyopathy; factors related to clinical severity, left ventricular dilation, systolic pulmonary artery pressure and duration of symptoms defined a subgroup of patients with poor prognosis.
Abstract: A study of factors predicting mortality was performed in 201 patients with dilated cardiomyopathy (163 men, 38 women, mean age: 48 +/- 11 years) by multivariate analysis (Cox Model) of 51 clinical, electrocardiographic, echocardiographic and haemodynamic parameters, 56 patients died during follow-up (mean follow-up: 57.1 +/- 29.9 months). 5 year survival was 77 +/- 3%. The following parameters were independent predictors of mortality: first symptom: pulmonary oedema, peripheral oedema, syncope; duration of symptoms at the time of inclusion; end systolic left ventricular volume; end diastolic left ventricular diameter; pulmonary artery systolic pressure; and their combination had the most accurate predictive value for death. A quantitative score (s) was calculated and used to define three subgroups: A:s less than or equal to 4.5; B: 4.5 less than s less than 6; C:s greater than or equal to 6. Five-year survival was 90 +/- 5% in group A; 84 +/- 4% in B and only 53 +/- 7% in C. In conclusion, overall survival was good in this population of all stage dilated cardiomyopathy; factors related to clinical severity, left ventricular dilation, systolic pulmonary artery pressure and duration of symptoms defined a subgroup of patients with poor prognosis.
124 citations
TL;DR: A large proportion of cardiac defects associated with TF consists of anomalies of coronary arteries, which confirm the usefulness of performing preoperatively routine coronary angiography in patients with complex congenital heart disease.
Abstract: Numerous studies have pointed out the frequent association of tetralogy of Fallot (TF) with other cardiovascular defects and coronary tree anomalies. We found cardiac defects in 181 (68%) out of 265 patients with TF investigated by catheterization and selective coronary angiography. These anomalies were isolated in 88 cases (49%) and associated with others in 93 patients. In the case of an isolated anomaly associated with TF, the coronary tree was involved in 37.5% and the cardiovascular system in the remaining 62.5%; in the case of two anomalies, the coronary system was involved in 66% of the patients and the cardiovascular apparatus in 34%; in the case of three or more anomalies, the coronary arteries were involved in 71% and the cardiovascular system in 29%. Anomalies in the course and/or distribution of coronary arteries were present in 96 patients (36%): 10 had a single coronary ostium, 13 a left anterior descending artery arising from the right coronary artery, one a circumflex artery arising from the right coronary artery. Small fistulas between coronary arteries and the pulmonary artery were found in 20 cases; anastomoses between coronary and bronchial arteries or right atrium in 42. In 39 patients we observed a large conus artery or large anterior ventricular branches crossing the right ventricle. A right aortic arch was found in 56 patients (21%), a stenosis of the trunk and/or the peripheral pulmonary artery in 35 (13%) and pulmonary artery atresia in five. Four patients showed a complete atrioventricular canal, three an atrial septal defect (primum type) with cleft of the mitral valve, 61 (23%) an atrial septal defect (ostium secundum). Eleven patients had anomalies of the systemic venous return, 26 (10%) a patent ductus arteriosus. Four patients had valvular abnormalities. In our series, a large proportion of cardiac defects associated with TF consists of anomalies of coronary arteries. Our data confirm the usefulness of performing preoperatively routine coronary angiography in patients with complex congenital heart disease.
121 citations
TL;DR: The present data show a decrease in cytochrome content and in cy tochrome-dependent enzyme activity in human dilated cardiomyopathy, and it is necessary to clarify whether these findings are specific for dilated heart failure or whether they are epiphenomena of failing hearts.
Abstract: The defects underlying the impairment of systolic pump function in human dilated cardiomyopathy (DCM) are not known. We isolated mitochondrial particles from 10 hearts of transplant recipients with DCM and from nine normal hearts not used for transplantation. Yield was similar in both groups (2.77 vs 2.81 mg mitochondrial protein per gram heart). Cytochrome content (difference spectrophotometry) was found reduced in DCM mitochondria, e.g. cytochrome c was 0.295 +/- 0.06 in the DCM group and 0.371 +/- 0.04 mumol g-1 in the control group (P less than 0.05). Enzymatic activity of the cytochrome-containing complexes III (3.77 +/- 0.82 vs 4.95 +/- 1.15 mumol min-1.mg-1) and IV (2.63 +/- 0.96 vs 3.65 +/- 0.6 mumol min-1.mg-1) of the respiratory chain was reduced in the DCM group (P less than 0.05). Complex IV, the cytochrome c oxidase, in the DCM group showed impaired activity also in whole heart homogenates (0.173 +/- 0.04 vs 0.258 +/- 0.8 mumol min-1.mg-1). Subunit composition of the cytochrome c oxidase on sodium dodecyl sulphate-gel electrophoresis did not differ between DCM and normal hearts. Activity of complexes II and V of the respiratory chain, not containing cytochromes, was unchanged in DCM mitochondria compared with the control group. The present data show a decrease in cytochrome content and in cytochrome-dependent enzyme activity in human dilated cardiomyopathy. Further studies are necessary to clarify whether these findings are specific for dilated cardiomyopathy or whether they are epiphenomena of failing hearts.
TL;DR: The hypothesis that decreasing the energy reserve for ATP synthesis renders the heart more susceptible to systolic and diastolic failure is supported.
Abstract: To address the hypothesis that impaired ATP synthesis rates caused by changes in the creatine kinase system is an important mechanism underlying cardiac failure, we measured total creatine kinase activity, isoenzyme composition and creatine content in two animal models of hypertrophy with cardiac dysfunction, the spontaneously hypertensive rat in the transition to failure and the creatine-depleted hyperthyroid rat heart challenged by hypoxia. During the transition from stable compensated hypertrophy to failure characterized by decreased functional capacity, we found that total creatine kinase activity and particularly mitochondrial creatine kinase activity decreased. The decrease in functional capacity, the further increase in heart size and the derangements in the creatine kinase system did not occur if these animals were treated for 6 months with the antihypertensive agents, guanethidine or hydralazine. These results suggest that changes in the creatine kinase system occur coordinately with the transition to failure. To assess whether the changes in the creatine system may be causally linked to decreased functional capacity, we used 31P NMR spectroscopy of isolated perfused hearts to define the high energy phosphate content and cardiac performance of creatine-depleted (approximately 50%) hypertrophied hearts challenged by hypoxia. These hearts displayed greater susceptibility to hypoxic injury with regard to both systolic and diastolic function during and following hypoxia. We also measured total creatine kinase activity in right ventricular biopsy specimens from patients with various forms of cardiomyopathy and low ejection fractions, and found a positive correlation between total creatine kinase activity and ejection fraction. Taken together, these results support the hypothesis that decreasing the energy reserve for ATP synthesis renders the heart more susceptible to systolic and diastolic failure.
TL;DR: It is concluded that a depressed fibrinolytic capacity attributable to a low tissue plasminogen activator activity is of pathogenetic importance for the development of myocardial infarction in patients with unstable angina pectoris.
Abstract: The balance between the coagulation system generating fibrin and its subsequent removal by the fibrinolytic system determines the fate of fibrin deposited in the vascular system. In a prospective study, selected haemostatic variables assessing this balance were determined in plasma samples from 20 consecutive patients admitted with unstable angina pectoris. Over a follow-up period of 6 years, eight patients developed myocardial infarction, whereas 12 patients did not. There was no significant difference between the two groups in the median plasma concentrations of thrombin-antithrombin III complexes reflecting the coagulant activity. The infarction group was characterized by a significantly lower median activity of tissue plasminogen activator in plasma euglobulins (P less than 0.05), a higher median concentration of tissue plasminogen activator antigen in plasma (P less than 0.05) and a tendency to higher plasma levels of antigenic and functional plasminogen activator inhibition. In all patients, the activities of tissue plasminogen activator inhibitor and of tissue plasminogen activator were significantly associated (rs = -0.4811, P less than 0.05). We conclude that a depressed fibrinolytic capacity attributable to a low tissue plasminogen activator activity is of pathogenetic importance for the development of myocardial infarction in patients with unstable angina pectoris.
TL;DR: Therapeutic interventions may reduce the marked sympathetic activation which occurs in heart failure, and in some instances (particularly with digitalis compounds) may also improve the impaired sensitivity of reflex cardiovascular control.
Abstract: This paper reviews the evidence that congestive heart failure is characterized by an increase in sympathetic nerve activity and that this may begin in an early symptomatic phase and progress with the severity of the disease. The sympathetic activation initially plays a compensatory role but eventually is outweighted by adverse consequences at both cardiac and vascular levels which may aggravate the clinical status and negatively affect prognosis. This is likely to depend on the fact that the sympathetic activation becomes excessive due to reduction in sensitivity of baroreflexes and cardiopulmonary reflexes restraining sympathetic tone (functional reflex denervation) and positive interactions between the sympathetic and the renin-angiotensin system. Therapeutic interventions may reduce the marked sympathetic activation which occurs in heart failure, and in some instances (particularly with digitalis compounds) may also improve the impaired sensitivity of reflex cardiovascular control.
TL;DR: To examine the reproducibility of cardiopulmonary exercise testing in patients with heart failure, three consecutive tests were performed in 30 patients, and the first test underestimated treadmill exercise time by about 20% when compared with the second and third tests, which were not significantly different.
Abstract: To examine the reproducibility of cardiopulmonary exercise testing in patients with heart failure, three consecutive tests were performed in 30 such patients. The first test underestimated treadmill exercise time by about 20% when compared with the second and third tests, which were not significantly different. Peak achieved VO, VCO,and VE were also less during the first test, but blood pressure, heart rate and respiratory rate responses were similar in the three tests. When cardiopulmonary exercise tests are used to assess functional capacity in either individual patients or groups (as in a therapeutic trial), at least two tests should be performed, as a single test is likely to underestimate exercise capacity.
TL;DR: An overview of the current understanding of the relation between plasma macromolecules and atherogenesis is presented and it is suggested that much of this fraction is accounted for by lipoprotein(a).
Abstract: This paper presents a brief overview of our current understanding of the relation between plasma macromolecules and atherogenesis. Plasma proteins enter normal intima by vesicular transport across normal endothelium, and convective transport within the intima; accumulation depends mainly on molecular size and the molecular sieve properties of the internal elastic lamina. Within the intima the proteins may be modified; particularly striking changes occur in high density lipoprotein (HDL) and in fibrinogen. Fibrinogen appears to be converted to fibrin which is then lysed, providing a continuing source of fibrin degradation products (FDP). Fibrin also seems to be associated with a tightly bound, plasmin-releasable apo-B-containing lipoprotein; work in progress suggests that much of this fraction is accounted for by lipoprotein(a).
TL;DR: Results from epidemiological studies have indicated that high plasma levels of lipoprotein (a) are an independent risk factor in the early development of arteriosclerosis and biochemical and immunohistochemical studies have demonstrated the presence of apolipoprotein ( a) in vessel wall tissue.
Abstract: We compared CHD patients with healthy blood donors to confirm the role of Lp(a) as an independent risk factor. More important, we performed biochemical and immunohistochemical studies to evaluate the potential mechanism by which Lp(a) causes CHD. We measured the Lp(a) concentration in comparison with other lipoprotein parameters in fresh human arterial wall biopsies and, in autopsy tissue, we localized apo (a) and apo B, as well as fibrin, with immunohistochemical methods in different vessel areas. Density gradient ultracentrifugation was used to analyse lipoprotein fractions isolated from human arterial wall. Lp(a) accumulates in the intima, preferentially in plaque areas, dependent on the serum Lp(a) level. Most of the Lp(a) can be located extracellularly, but apo(a) can also be detected in foam cells. A strong co-localization has been observed for apo(a) and apo B; only a few areas containing only apo B were detected. Moreover, a striking co-localization for apo(a) and fibrin was found. The possibilities for the pathways by which Lp(a) enters the arterial wall and accumulates extracellularly are discussed on the basis of the present data and recent data published by other groups.
TL;DR: The systolic time intervals offer temporal description of the sequential phases of cardiac cycle which are influenced physiologically by the same variables as affect other measures of left ventricular (LV) performance.
Abstract: The systolic time intervals (STI) offer temporal description of the sequential phases of cardiac cycle which are influenced physiologically by the same variables as affect other measures of left ventricular (LV) performance. The STI hence offer a measure of ventricular function which augments other measures of ventricular performance. Because of the extreme sensitivity of this variable and the ease of its measurement the STI are well suited for studying the effect of pharmacologic agents upon the heart.
TL;DR: The findings support the conclusion that at least a portion of the LDL isolated from atherosclerotic lesions is similar, if not identical, to oxidatively modified LDL.
Abstract: Each method used for the extraction and isolation of intimal lipoproteins has advantages and disadvantages. Gentle extraction methods are needed to characterize subtle modifications in the structure and biologic properties of the lipoproteins, whereas more aggressive methods are needed if the goal is to maximize the yield of lipoproteins from atherosclerotic arteries. The present paper evaluates different methods used for the isolation of intima1 lipoproteins.
Normal intima contains remnant-like and low density lipoprotein (LDL)-like particles that more strongly stimulate cholesterol esterification in macrophages than do control plasma LDL. Both fractions contain apolipoprotein (apo) E but neither shows clear signs of oxidative modification.
LDL-like particles from atherosclerotic lesions, on the other hand, contain malondialdehyde- and 4- hydroxynonenal-lysine adducts in apo B, are chemotactic for monocytes and show increased degradation in macrophages, a process that oxidized LDL prepared in vitro can compete with. The findings support the conclusion that at least a portion of the LDL isolated from atherosclerotic lesions is similar, if not identical, to oxidatively modified LDL.
TL;DR: Age and ambulatory blood pressure, but not sex, duration of hypertension, clinic blood pressure and left ventricular mass itself, were the major independent determinants of these abnormalities in essential hypertension.
Abstract: The independent contribution of age, sex, duration of hypertension, heart rate, clinic and ambulatory blood pressure and echocardiographic left ventricular mass to left ventricular diastolic filling abnormalities in essential hypertension was investigated in 250 subjects (145 untreated and unselected hypertensives and 105 healthy normotensive controls) undergoing Doppler and standard echocardiography and non-invasive 24-h ambulatory blood pressure monitoring. Late and early diastolic transmitral peak flow velocities and their ratio (all P < 0.01), the rate of deceleration of early diastolic mitral flow (P < 0.01) and the time of deceleration of early diastolic mitral flow (P = 0.018) were abnormal in the hypertensive group vs controls. None of these parameters significantly varied in the presence vs absence of LV hypertrophy.
In the hypertensive group, the prevalence of abnormal age-corrected Doppler values varied up to 46% (up to 45.4% and 50% in the absence and presence of left ventricular hypertrophy, respectively; P = n.s.). In a stepwise multivariate regression analysis, age and average daytime or night-time ambulatory blood pressure showed a significant independent relationship with each of these Doppler indexes of left ventricular diastolic filling. Late transmitral peak flow velocity and the ratio of late to early peak flow velocity were also independently affected by the heart rate. Sex, duration of hypertension, clinic systolic and diastolic blood pressure and left ventricular mass index did not show any independent relationship to these Doppler parameters of left ventricular filling.
In conclusion, Doppler abnormalities of diastolic transmitral blood flow were detected in up to 46% of patients in an unselected hypertensive population with a low prevalence (14.5%) of left ventricular hypertrophy. Age and ambulatory blood pressure, but not sex, duration of hypertension, clinic blood pressure and left ventricular mass itself, were the major independent determinants of these abnormalities.
TL;DR: Doppler methods are safe, fairly reproducible and reasonably accurate methods for measuring cardiac output in selected patients provided signal quality is adequate during recording.
Abstract: The Doppler ultrasonic estimation of cardiac output in man is reviewed. Minimal requirements for accurate measurements are discussed, and the published results of reproducibility studies and validation studies are summarized and analysed. Analysis of Doppler records has a coefficient of repeat determination of 5-8% for aortic or LV outflow tract measurements and this is higher for other sites. Short-term variability varies from 4 to 10%, and that over days to weeks from 9 to 14%. Thus a single measurement may vary up to +/- 28% over time with no true change in cardiac output. For cardiac output determination, the Doppler methods show accuracies varying from 10 to 22% (coefficient of variation of the differences between methods) indicating that a single aortic based measurement only reliably lies within +/- 28% compared with other 'standard' methods, and during exercise the accuracy is less (+/- 44%). Doppler methods are safe, fairly reproducible and reasonably accurate methods for measuring cardiac output in selected patients provided signal quality is adequate during recording.
TL;DR: In patients with infective endocarditis, anticoagulation with heparin should be maintained whenever a brain infarct is present, unless it is large and/or haemorrhagic.
Abstract: Anticoagulation is still a matter of debate in infective endocarditis, since it can increase the risk of complications, mostly neurological. In our series of 269 patients with native valve endocarditis studied between 1970 and 1982, 35 were anticoagulated. We observed 14 patients with brain infarcts, of whom five died, and 12 patients with cerebromeningeal or brain haemorrhage of whom six died. In a similar series of 63 patients with prosthetic valve endocarditis, all of whom were on anticoagulation and were studied between 1972 and 1987, we observed five patients with brain infarcts, three of whom died, and two patients with brain haemorrhage, one of whom died. The frequency of cerebrovascular accident (CVA) was similar for both groups (11.1% in prosthetic endocarditis vs 11.5% in native valve endocarditis, P = ns), as was mortality rate (57% vs 48.4%, P = ns). CVA are significantly more frequent among anticoagulated patients (19/94 vs 19/238: P less than 0.01), but the mortality rate in CVA is similar for anticoagulated and non-anticoagulated patients (11/19 vs 8/19: P = ns). The indications for anticoagulation in infective endocarditis remain similar to those in valvular heart disease. In patients with infective endocarditis, anticoagulation with heparin should be maintained whenever a brain infarct is present, unless it is large and/or haemorrhagic.
TL;DR: The cardiogreen method is probably one of the most accurate methods to study cardiac output during exercise and has been extensively used in the laboratory to study changes in central haemodynamics in essential hypertension at rest and during exercise, and also to study the haemodynamic alterations induced by anti-hypertensive agents.
Abstract: The dye dilution method for measuring cardiac output is based on injecting rapidly a known quantity of a dye at one site into the circulatory system, and withdrawing blood at a distal site for determination of a concentration curve of the dye. Flow (Q) is calculated by the formula: (formula: see text) where m is the amount of dye injected, c mean concentration of dye and t the time of the concentration curve without recirculation. In recent years the only dye used has been indocyanine green (cardiogreen) which has its absorption maximum in the infrared part of the spectrum (at 805 microns) - where oxyhaemoglobin and reduced haemoglobin transmit light equally. Several densitometers for cardiogreen have been developed. The Christian Michelsen Institute densitometer used in our laboratory was found to give very accurate measurements (error less than +/- 2%) of blood flow in model experiments, for flows ranging from 2 to 12 l min-1. The more modern densitometers are usually equipped with computers. The cardiogreen method is probably one of the most accurate methods to study cardiac output during exercise. The error of a single determination of cardiac output values at rest and during exercise is less than +/- 5%. The method does not allow measurement of 'beat to beat' changes, and requires a cardiac output which is stable for approximately 10 s during exercise and 30 s at rest. It has been extensively used in our laboratory to study changes in central haemodynamics in essential hypertension at rest and during exercise, and also to study the haemodynamic alterations induced by anti-hypertensive agents.(ABSTRACT TRUNCATED AT 250 WORDS)
TL;DR: Fast Fourier Transform analysis was used to study ventricular fibrillation induced by several different methods in 43 greyhounds anaesthetized with sodium pentobarbitone, finding little difference in the time-course of fibrilation in the non-ischaemic heart recorded directly from the epicardium or from a surface lead.
Abstract: Fast Fourier Transform analysis was used to study ventricular fibrillation induced by several different methods in 43 greyhounds anaesthetized with sodium pentobarbitone. The dominant frequency at the body surface of ventricular fibrillation induced electrically in non-ischaemic hearts was initially 9-9 ±0-7 Hz, remained above 9 Hz for 70 s and then rapidly fell to 5 Hz. The dominant frequency of ventricular fibrillation induced by acute occlusion (initially 12-3 ± 0-2 Hz), or by reperfusion (12-2 + 0-4 Hz) of the anterior descending branch of the left coronary artery, showed a similar time-course. However, ventricular fibrillation induced by administration of potassium (4-8±0-8 Hz) or ouabain (7-1 ± 11 Hz) was significantly slower. Fibrillation recordedfrom the endocardium of the heart initially showed a similar dominant frequency to that recorded at the body surface, but there was no significant fall in frequency over 3-3 mins. There was little difference in the time-course of fibrillation in the non-ischaemic heart recorded directly from the epicardium or from a surface lead. These findings may be of relevance to the poor response to DC countershock after prolonged ventricular fibrillation, hyperkalaemia or cardiac glycosides.
TL;DR: The development of echocardiography has permitted non-invasive estimation of left ventricular stroke volume and cardiac output, albeit with some limitations, which are particularly suited to hypertensive patients.
Abstract: The development of echocardiography has permitted non-invasive estimation of left ventricular stroke volume wid cardiac output, albeit with some limitations. These approaches are particularly suited to hypertensive patients.
TL;DR: A removable vena cava filter that may be introduced percutaneously, is atraumatic to the venous wall, and permits the simultaneous use of thrombolytic therapy is presented, which allows an effective temporary filtering of the venacava.
Abstract: The authors present a removable vena cava filter that may be introduced percutaneously, is atraumatic to the venous wall, and permits the simultaneous use of thrombolytk therapy. Sixty-five patients were studied: 42 cases of pulmonary embolism with threatening venous thrombosis; 23 cases of phlebitis associated with an ilio-caval thrombus without pulmonary embolism. The filter was introduced 38 timesfemor ally and 27 times by a jugular approach. In 16 cases (24-6%) clots broke loose, were effectively caught by the filter, and were progressively dissolved during thrombolytic therapy. The filter remained in place on average 4-5 ± 1-2 days. The filter was removed in all cases without provoking the recurrence of pulmonary embolism. Two deaths, not related to pulmonary embolism, occurred during hospitalization. Phlebography, performed in all cases before and after treatment, showed a significant decrease of the phlebographic score (10.88±0.82 vs 6.77±0.86, P<0001). The same was observed in 40 patients who underwent a pulmonary angiography before and after treatment (Miller index = 1704 ±0.73 vs 5.49 ±0.87, P<00001). After removal of the filter, no sign of pulmonary embolism was detected on lung scan in the 23 patients with ilio-caval thrombus alone. More than 5 g (100ml)−1l of haemoglobin was lost by 15.38% of patients. All patients were follow ed-up for a mean of 712± 1.3 months; in no case was there any clinical recurrence of pulmonary embolism. Thus this device allows an effective temporary filtering of the vena cava. Thrombolytic therapy, in association with the retrievable filter is possible with favourable results at the cost of an increased risk of haemorrhage.
TL;DR: Retrospective data regarding 290 patients suffering from spontaneous aortic dissection between January 1976 and June 1987 are reported and it is demonstrated that acute myocardial infarction, persistent shock and persistent central neurologic deficit were significant independent predictors of operative mortality in type A patients.
Abstract: Retrospective data regarding 290 patients suffering from spontaneous aortic dissection between January 1976 and June 1987 are reported Dissection was always documented by retrograde aortography and data were collected from 11 catheterization laboratories operating in North-East Italy The results show that over a 12-year period there was an increase in cases, an increase in the number of operations and a decline in operative mortality Multivariate discriminant analysis demonstrated that acute myocardial infarction, persistent shock and persistent central neurologic deficit were significant independent predictors of operative mortality in type A patients Only persistent shock was significantly related to higher operative mortality in type B patients Late deaths occurred in 14/118 operated patients, and were mostly secondary (directly or indirectly) to aortic dissection Discharged patients underwent frequent medical checks and chronically received drugs to control hypertension and reduce inotropism Most of them (737%) were asymptomatic: careful post-operative medical assistance is necessary to guarantee the long-term success of surgical treatment
TL;DR: Results from CAST answered the hypotheses posed for flecainide and encainide in that suppression of frequent PVCs by those two drugs did not favorably influence outcome, and significantly worsened the total sudden death mortality compared with placebo overall and across all subgroups analyzed.
Abstract: F requent and repetitive forms of premature ventricular complexes (PVCs) have been recognized as independent markers of increased risk for sudden cardiac death in patients with a previous myocardial infarction. On this basis, the Cardiac Arrhythmic Suppression Trial (CAST) was initiated to test the hypothesis that suppression of these ventricular arrhythmias would reduce the incidence of sudden cardiac death.1 As critically reviewed by Furberg,2 previous studies with antiarrhythmic drugs in post-myocardial infarc-tion patients were seriously flawed in one or more ways, such that they could not conclusively demonstrate whether suppression of ventricular arrhyth-mias by the antiarrhythmic drugs studied affected survival. CAST, a placebo-controlled, double-blind, multi-center study, was initiated in June 1987 to evaluate the effect of three antiarrhythmic drugs (encainide, flecainide, and moricizine) in patients who had sustained a myocardial infarction and had asymptomatic or mildly symptomatic ventricular arrhythmias. Approximately 22 months after its initiation, part of the study was prematurely halted, and the remaining part was significantly modified because of excessive mortality in the group of patients randomized to treatment with encainide or flecainide.1 The study is continuing with the third drug, moricizine. CAST is an important study for several reasons. For the first time, convincing data were provided regarding a mode of antiarrhythmic treatment that existed for some 20 years and was widely applied by practicing physicians. The results of CAST may lead to extensive changes in antiarrhythmic therapy, and they merit careful consideration. Also, results from CAST answered the hypotheses posed for flecainide and encainide in that suppression of frequent PVCs by those two drugs did not favorably influence outcome. On the contrary, despite effective suppression of PVCs, flecainide and encainide significantly worsened the total sudden death mortality compared with placebo overall and across all subgroups analyzed. Thus, the study answered the main question for these two drugs. However, several questions remain, and many new concerns have been generated, including questions about the scientific and medical implications of the CAST results, therapeutic implications concerning the use of these drugs for management of patients with other arrhythmias, extrapolation of these data to the use of other antiarrhythmic drugs, implications for regulatory authorities, and implications for future studies and new drug development. To address some of these issues, the Working Group on Cardiac Arrhythmias of the European Society of Cardiology convened a task force committee. CAST produced surprising results surprisingly early. There was definite evidence of harm after 10 …
TL;DR: The haemodynamics and myocardial lactate consumption during induced atrial fibrillation (AF) were studied in 10 patients with paroxysmal AF and the haemodynamic changes during AF were similar to those seen during regular ventricular pacing at an equivalent rate.
Abstract: The haemodynamics andmyocardiallactate consumption during induced atrial fibrillation (AF) were studied in 10 patients with paroxysmal A F. Their mean age ( ± SD) was 61 ± 5 years and none had clinical evidence of ischaemic or rheumatic heart disease. Compared with sinus rhythm, the onset of AF was associated with a reduction in systolic blood pressure (152± 13 mmHg) in AF vs 169±23 mmHg in sinus rhythm, P>0-01). There was no consistent change in cardiac output at the onset of AF compared with sinus rhythm, but the cardiac output was lower compared with regular atrial pacing at rates similar to those of induced AF (3-85±0-76vs4-38±0-89lmin-', P>002). Compared with sinus rhythm or rate-matched atrial pacing, AF was associated with an elevated pulmonary arterial pressure (24-2±5-6 mmHg in AF vs 17-9±14-4 mmHg in sinus rhythm, P>001) and pulmonary arterial wedge pressure (18-6±5-6 vs 9-7±3-9mmHg, P>0-01). The haemodynamic changes during AF were similar to those seen during regular ventricular pacing at an equivalent rate, although the latter was associated with a lower systolic blood pressure (152±13 mmHg in AF vs 136±25 mmHg in ventricular pacing, P>005) and higher right atrial pressure (8-2±4-4 vs 11-5±7-5 mmHg respectively, P>0-05), presumably due to the deleterious effects of cannon 'a' waves. Myocardial lactate extraction was similar during sinus rhythm, atrial pacing and AF, but tended to be higher during regular ventricular pacing. In conclusion, in the absence of structural heart disease, the development ofA Fwas associated with minimal change in systemic pressure and cardiac output, but substantial change in the left ventricular filling pressure due to the absence of an effective atrial contraction. AF appears to be better tolerated than rate-matched ventricular pacing with atrio-ventricular dysynchrony.
TL;DR: Optimal therapy of heart failure should, therefore, also aim at improving this phase of the cardiac cycle, since impaired relaxation and reduced diastolic distensibility are almost universal in chronic congestive heart failure.
Abstract: Myocardial relaxation is an energy-dependent process. Indeed, adenosine triphosphate (ATP) is required to pump free myoplasmic calcium back into the sarcoplasmic reticulum. It is also necessary to extrude the calcium ions which enter the cell during the plateau phase of the action potential. The calcium-sodium exchange mechanism does not seem to require energy in itself, but sodium exchanged for calcium eventually needs to be extruded via sodium/potassium ATPase and there is also an ATP-dependent calcium pump. Thus, when ATP production is limited, calcium may remain fixed to troponin for part or for the whole of diastole, resulting in a slower rate of isovolumic relaxation and reduced distensibility of the myocardium. Alterations in diastolic function caused by inadequate energy production occur in the high-demand type of myocardial ischaemia. There is also growing evidence that most forms of heart failure are accompanied by a state of energy depletion. Alterations in mitochondrial density and enzymatic activity are common in the failing myocardium and may partially explain the reduction in ATP production. Inadequate growth of the capillary network in hypertrophied myocardium, impaired subendocardial perfusion due to increased diastolic wall stress and/or coronary artery disease, probably also contribute to an imbalance between energy production and utilization. As relaxation is intrinsically a much slower process than activation and since changes in ATP concentration may also affect calcium efflux by allosteric effects, impaired relaxation and reduced diastolic distensibility are almost universal in chronic congestive heart failure. Optimal therapy of heart failure should, therefore, also aim at improving this phase of the cardiac cycle.