Prospective multicenter study of pregnancy outcomes in women with heart disease.

BACKGROUND: The maternal and neonatal risks associated with pregnancy in women with heart disease receiving comprehensive prenatal care have not been well defined. METHODS AND RESULTS: We prospectively enrolled 562 consecutive pregnant women with heart disease and determined the outcomes of 599 pregnancies not ending in miscarriage. Pulmonary edema, arrhythmia, stroke, or cardiac death complicated 13% of pregnancies. Prior cardiac events or arrhythmia, poor functional class or cyanosis, left heart obstruction, and left ventricular systolic dysfunction independently predicted maternal cardiac complications; the cardiac event rate can be predicted using a risk index incorporating these predictors. Neonatal complications (20% of pregnancies) were associated with poor functional class or cyanosis, left heart obstruction, anticoagulation, smoking, and multiple gestations. CONCLUSIONS: Pregnancy in women with heart disease is associated with significant cardiac and neonatal complications, despite state-of-the-art obstetric and cardiac care. Maternal cardiac risk can be predicted with the use of a risk index.

Haemodynamic and ADH responses to central blood volume shifts in cardiac-denervated humans.

Haemodynamic responses and antidiuretic hormone (ADH) were measured during body position changes designed to induce blood volume shifts in 10 cardiac transplant recipients to assess the contribution of cardiac and vascular volume receptors in the control of ADH secretion. Each subject underwent 15 min of a control period in the seated posture, then assumed a lying posture for 30 min at 6 degrees head-down tilt (HDT) followed by 30 min of seated recovery. Venous blood samples and cardiac dimensions (echocardiography) were taken at 0 and 15 min before HDT, 5, 15 and 30 min of HDT, and 5, 15 and 30 min of seated recovery. Blood samples were analysed for haematocrit, plasma osmolality, plasma renin activity (PRA) and ADH. Resting plasma volume (PV) was measured by Evans blue dye and per cent changes in PV during posture changes were calculated from changes in haematocrit. Heart rate (HR) and blood pressure (BP) were recorded every 2 min. In the cardiac transplant subjects, mean HR decreased (BP less than 0.05) from 102 b.p.m. pre-HDT to 94 b.p.m. during HDT and returned to 101 b.p.m. in seated recovery while BP was slightly elevated (P less than 0.05). PV was increased by 6.3% (P less than 0.05) by the end of 30 min of HDT but returned to pre-HDT levels following seated recovery. Plasma osmolality was not altered by posture changes. Mean left ventricular end-diastolic volume increased (P less than 0.05) from 90 +/- 5 ml pre-HDT to 105 +/- 4 ml during HDT and returned to 88 +/- 5 ml in seated recovery. Plasma ADH was reduced by 28% (P less than 0.05) by the end of HDT and returned to pre-HDT levels with seated recovery. PRA was also reduced by 28% (P less than 0.05) with HDT. These responses were similar to those of six normal cardiac-innervated control subjects and one heart-lung recipient. Therefore, cardiac volume receptors are not the only mechanism for the control of ADH release during acute blood volume shifts in man.

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

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

Respiratory metabolism of L-929 cells at different water contents and volumes.

Oxygen consumption was measured in mouse L-929 cells whose volumes and water contents were reduced by adding sorbitol to the medium. The volume of water lost due to a given sorbitol supplement exceeded the loss in apparent cell volume. An explanation is given for this discrepancy. The rate of oxygen uptake in the absence of exogenous respiratory substrate was essentially the same in cells whose total volume was reduced by 45%, amounting to a loss of about 70% of the total cell water, compared to controls at 'physiological' volume and water content. Cells under these same conditions responded to added substrates (pyruvate, glucose, and glutamine) and inhibitors (iodoacetate and 2-deoxyglucose) in nearly the same way as control cells. These observations are in accord with and add to previous work showing that very large fluctuations in cell volume and water content have only modest effects on the rates and directions of a variety of metabolic processes. The results are interpreted in terms of current views on the composition and organization of the aqueous compartments of eucaryotic cells.

Exercise training during long-term beta-blockade treatment in healthy subjects.

Although it is well accepted that treatment with beta-blocking drugs impairs endurance exercise capacity acutely, whether a trained state can be achieved while receiving long-term beta-blocker therapy is controversial. The apparent attenuation of training reported in some studies has given rise to the theory that adrenergic stimulation represents a unifying mechanism by which endurance training effects are produced. This theory is supported by studies of long-term beta-agonist infusions that show apparent training responses. To assess the role of beta-adrenergic stimulation produced by exercise in the development of cardiovascular training effects, 39 healthy men were assigned in a random, double-blind fashion to receive oral propranolol, atenolol or matched placebo. Drug doses were titrated individually to minimize the heart rate response to submaximal exercise (dose ranges: atenolol, 50 to 200 mg/day; propranolol, 160 to 320 mg/day). After beginning chronic drug administration, all subjects participated in an intense, supervised 6-week exercise training program (5 days/week, 45 min/day, at least 75% peak heart rate). Adherence to training was monitored by daily supervision; compliance to the medication regimen was assessed by weekly pill counts, medication diaries and plasma drug assay. Maximal exercise testing was performed before and after training. Peak oxygen consumption increased significantly with training in all 3 groups, whether comparisons were made in the presence or absence of medication. The magnitude of change in oxygen consumption did not differ between groups (F = 0.12, p greater than 0.88). Similarly, peak work rate and duration of work increased in all 3 groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Changes in rest and exercise myocardial perfusion and left ventricular function 3 to 26 weeks after clinically uncomplicated acute myocardial infarction: effects of exercise training.

The effects of exercise training on exercise myocardial perfusion and left ventricular (LV) function in the first 6 months after clinically uncomplicated acute myocardial infarction (AMI) were assessed in 53 consecutive men aged 55 +/- 9 years. Symptom-limited treadmill exercise with thallium myocardial perfusion scintigraphy and symptom-limited upright bicycle ergometry with equilibrium gated radionuclide ventriculography were performed 3, 11 and 26 weeks after AMI by 23 men randomized to training and 30 randomized to no training. Peak cycle capacity increased in both groups between 3 and 26 weeks (p less than 0.01), but reached higher levels in trained than in untrained patients (803 +/- 149 vs 648 +/- 182 kg-m/min, p less than 0.01). Reversible thallium perfusion defects were significantly more frequent at 3 than at 26 weeks: 59% and 36% of patients, respectively (p less than 0.05), without significant inter-group differences. Values of LV ejection fraction at rest, submaximal and peak exercise did not change significantly in either group. The increase in functional capacity, i.e., peak treadmill or bicycle workload, that occurred 3 to 26 weeks after infarction was significantly correlated with the increase in peak exercise heart rate (p less than 0.001), but not with changes in myocardial perfusion or LV function determined by radionuclide techniques. Changes in myocardial perfusion or LV function do not appear to account for the improvement in peak functional capacity that occurs within the first 6 months after clinically uncomplicated AMI.

Computerized quantitative analysis of left ventricular wall motion by two-dimensional echocardiography.

Quantitative detection of left ventricular segmental wall motion abnormalities by any modality depends on the reference system used because of the dynamic geometry of contraction and cardiac motion within the thorax. To assess the feasibility and accuracy of quantitative analysis of left ventricular wall motion by two-dimensional echocardiography, we studied 61 subjects with the use of 44 different reference methods in each of three echocardiographic views: the parasternal short-axis view at the levels of the mitral valve and of the papillary muscles and an apical four-chamber view. The three major groups of reference systems used were those with a fixed external reference, a floating reference correcting for translation, and systems correcting for both translation and rotation. In the first part of this study the end-diastolic and end-systolic outlines of 20 normal subjects were stored in a computer and composite data of these 20 subjects were plotted to obtain a 95% confidence interval for measured normal fractional change for each reference method. In the second part of the project an additional prospective group of 10 normal subjects and a group of 31 "abnormal" patients had their left ventricular wall motion analyzed by similar methods and the results were compared with all the confidence intervals. One reference method was selected for each two-dimensional echocardiographic view based on the highest sensitivity and specificity found by statistical analysis; a floating-reference system including translation was found to be optimal for the apical four-chamber and parasternal short-axis views at the level of the mitral valve and a fixed external reference system was optimal for the short-axis view at the papillary level. The percent fractional shortening of radial dimensions (radial methods) and the percent fractional change in area measurements (area methods) during the cardiac cycle were also calculated at 5, 10, 20, 30 and 45 degree intervals around the outline perimeter for each subject according to each of the 44 different methods. Area methods yielded the same specificity and sensitivity as radial dimension analysis methods at 5 to 45 degree intervals. Ten normal subjects underwent repeat echocardiography within 2 days of their first study to examine day-to-day variation. Average change in mean contraction from day to day was 7% to 9% for radial methods and 9% to 13% for area methods. In conclusion, we present a computerized system for unbiased selection of optimal methods of analysis of left ventricular wall motion by two-dimensional echocardiography.(ABSTRACT TRUNCATED AT 400 WORDS)

Lymphoma of the heart.

A case of malignant lymphoma involving the heart is reported. The patient presented with symptoms of cardiac decompensation. The echocardiographic findings of an echogenic mass arising from the pulmonary valve as well as demonstration of soft tissue density diffusely infiltrating the heart and mediastinum was confirmed by computer tomography and angiography. Although the findings on the noninvasive studies were highly indicative of tumor involvement, the temporal association of the symptoms to a motor vehicle accident lead to the erroneous diagnosis of intracardiac and mediastinal hematoma.

Standardized intracardiac measurements of two-dimensional echocardiography.

Thirty-five healthy adults were studied by two-dimensional echocardiography to attempt to standardize a simple method for measurement of intracardiac dimensions. Both ventricles and the atria and aorta were measured in five different views: parasternal long-axis, parasternal short-axis at the level of the aortic valve, the chordae tendineae and the papillary muscles and an apical four chamber view. The minor axis of each chamber was measured in all five views; the major axis in the apical four chamber view also was measured. All measurements are presented as a range of values (mean and 2 standard deviations about the mean); the mean value is given as well as the absolute range of values measured. Normalization according to body surface area is also presented. Data from these multiple views allow assessment of asymmetry of cardiac chambers in normal subjects. The mean minor axis dimension at end-diastole of the right ventricle in the parasternal long-axis view (1.9 to 3.8 cm) was 13.6% smaller than in the four chamber view (2.2 to 4.4 cm), whereas the minor axis dimension of the left ventricle in the parasternal long-axis view (3.5 to 6.0 cm) was only 1.1% larger than in the four chamber view (3.3 to 6.0 cm). Therefore, the right ventricular minor axis dimensions are not interchangeable. Reproducibility in 10 subjects for all dimensions showed a maximal variability of 4.8%. These values permit a standardized and expeditious method for measuring intracardiac dimensions by two-dimensional echocardiography.

Reproducibility of left ventricular volumes by two-dimensional echocardiography.

Reproducibility may be as important as absolute accuracy in assessing the utility of an echocardiographic method of left ventricular volume estimation for epidemiologic or physiologic studies. The magnitude of differences between measurements in the same subjects from day to day must be defined before any quantitative technique can be used reliably to document "real" changes in heart volume over time. Two-dimensional echocardiograms were performed serveral days apart in 30 subjects, including 20 normal subjects and 10 patients with stable coronary heart disease. Analyses of light-pen tracings provided measurements of end-diastolic volume, endsystolic volume and derived ejection fraction on both days, and differences in individual subjects between days were quantitated. Beat to beat, interobserver and intraobserver variability also were assessed. Although group values changed little from day to day, individual volume changes were substantial in some cases. Confidence limits for individual measurements were derived from analyses of intrasubject variability and were as follows: end-diastolic volume +/- 15%, end-systolic volume +/- 25%, ejection fraction +/- 10%. Confidence limits in a larger group of subjects were narrower; in a group of 30 subjects, changes of greater than 2% in end-diastolic volume, 5% in end-systolic volume and 2% in ejection fraction most likely represent real change. Intraobserver variability was minimal, but interobserver and beat to beat variability were of sufficient magnitude to suggest that serial measurements on a given subject be made ideally by a single person and that several cycles be averaged for a given measurement.

Temporal arteritis: cerebrospinal fluid and brain scan abnormalities (case report).

A 61-year-old man presented with a syndrome suggesting temporal arteritis. Abnormal radioisotope brain scan and cerebrospinal fluid (CSF) findings were consistent with a diagnosis of intracranial vasculitis. Although the clinical response to steroids was dramatic, improvement in the CSF abnormalities lagged. Nevertheless, persistent use of steroids in high dosage resulted in normalization of both CSF and brain scan abnormalities.