Alterations in left ventricular mass and performance in patients treated effectively for thyrotoxicosis. A comparative echocardiographic study.

The effect of successful therapy for thyrotoxicosis on left ventricular mass in human subjects has not been documented. Furthermore, assessment of intrinsic left ventricular pathophysiologic changes associated with hyperthyroidism has been limited by the difficulty of justifying invasive studies in these patients. Echocardiography is a suitable method of assessing cardiac dimensions and function in patients with thyrotoxicosis.Echocardiographic studies were performed on 15 thyrotoxic patients, mean age 36 years, prior to and 12 months after the initiation of effective antithyroid therapy. The clinical diagnosis and results of therapy were confirmed by the measurement of serum thyroxine levels. Therapy produced a significant decrease in heart rate (108 to 78 beats/min; p < 0.001), arterial pulse pressure (60 to 45 mm Hg; p < 0.02) and echocardiographically estimated cardiac output (6.49 to 3.84 liters/min; p < 0.001).There was a significant reduction in left ventricular mass from 135 to 96 g (p < 0.001). The mean velocity of circumferential fiber shortening was reduced from 1.13 to 0.81 cire/sec (p < 0.001), a change that correlated significantly with the decrease in heart rate (r = 0.66, p < 0.01). A minimal reduction in left ventricular diameter was found (4.7 to 4.5 cm; p < 0.05), whereas end-systolic diameter and shortening fraction remained unchanged. Four patients failed to repond to initial antithyroid therapy. The size of the left ventricular mass increased in these patients after unsuccessful therapy.This study shows that effective treatment for thyrotoxicosis is associated with a reduction in the size of the left ventricular mass. The correlation between alterations in heart rate and mean velocity of circumferential fiber shortening following effective therapy suggests that the changes in myocardial contractility in these hyperthyroid patients may be predominantly a negative chronotropic effect. Minimal changes in end-diastolic diameter without changes in end-systolic diameter tend to confirm that myocardial contractility is altered by the state of thyroid activity independent of the Frank-Starling mechanism.     

Clinical recognition of giant left ventricular aneurysm

The noninvasive diagnosis of left ventricular aneurysm has markedly improved with gated blood pool scintigraphy. However, in patients with giant anterior ventricular aneurysms, the gated blood pool scintigram performed in two standard views (anterior and 40 degree left anterior oblique) may incorrectly suggest ischemic cardiomyopathy. We retrospectively identified five patients who underwent resection of a ventricular aneurysm over a $\text{2}\text{1}\text{2}$ year period and who had preoperative scintigraphic studies that appeared to show severe diffuse left ventricular dysfunction. Contrast ventriculography demonstrated preserved wall motion in septal, inferior and lateral segments not seen by gated blood pool scintigraphy and showed extraordinarily large anterior aneurysms. M-mode or two-dimensional echocardiograms showed intact posterior wall function in all patients, suggesting severe regional myocardial disease rather than global dysfunction. Two-dimensional echocardiography showed additional segments with preserved function as well as discrete aneurysms in all patients. We conclude that gated blood pool scintigraphy, when performed in two standard views, may fail to correctly diagnose some patients with very large anterior wall aneurysms. M-mode echocardiography, two-dimensional echocardiography and additional scintigraphic views that visualize the posterior portions of the left ventricle improve noninvasive diagnosis of patients with resectable giant left ventricular aneurysms.     

Evaluation of left ventricular function in patients with sickle cell anemia

The echocardiographic measurements of cardiac chamber dimension, ejection phase indices of left ventricular function and the systolic time intervals of 23 adult patients with sickle cell anemia were compared to those of normal control subjects. Patients with sickle cell anemia had a significantly greater mean left ventricular systolic dimension index, left ventricular diastolic dimension index, left ventricular mass, stroke volume index, interventricular septal width, aortic root index and left atrial index. No significant differences were noted between the mean velocity of circumferential fiber shortening, ejection fraction or systolic time intervals. The anemic population was divided into two groups; one consisting of patients less than 30 years old and the other of patients over 30 years old. There were no significant differences between the ventricular dimensions, velocity of circumferential fiber shortening, ejection fraction and systolic time intervals of the two groups. These data indicate that the chronic volume overload of sickle cell anemia is well tolerated without development of left ventricular dysfunction.     

"Optimal" left ventricular filling pressure during nitroprusside infusion for congestive heart failure

On the basis of preload manipulations, an optimal left ventricular filling pressure of 14 to 18 mm Hg has been suggested for patients with left ventricular failure. Since afterload reduction results in increased cardiac output in heart failure, the hypothesis that left ventricular filling pressure could be reduced to normal by nitroprusside without compromising cardiac output was tested in 15 patients with acutely decompensated chronic congestive heart failure. Cardiac index was measured after each 4 to 6 mm Hg decrease in pulmonary wedge pressure until the latter fell below 14 mm Hg (Group I, nine patients) or until systolic arterial pressure reached 90 mm Hg during nitroprusside infusion (Group II, six patients). In Group I, pulmonary wedge pressure fell in significant decrements (p < 0.001) from 28 ± 4 (SD) to 24 ± 3, 17 ± 2, and 11 ± 2 mm Hg during nitroprusside infusion. Cardiac index rose in significant increments (p < 0.05) from 2.5 ± 0.8 to 2.8 ± 0.6, 3.3 ± 0.7, and 3.7 ± 1.1 liter/minute/m² with each increase in nitroprusside dosage. Mean arterial pressure fell during nitroprusside infusion from 97 ± 16 to 70 ± 8 mm Hg (p < 0.001) without any change in heart rate. In Group II, directionally identical changes in hemodynamics were observed during nitroprusside infusion; the highest cardiac index occurred at the lowest pulmonary wedge pressure attained, and no side effects were observed despite the fall in systolic arterial pressure to 90 mm Hg. Thus, reduction of left ventricular filling pressure to within the normal range by nitroprusside infusion in patients with chronic left ventricular failure can raise cardiac output beyond levels observed at left ventricular filling pressures of 14 to 18 mm Hg. Normalization of filling pressure may improve subendocardial coronary perfusion, and invasive monitoring of filling pressure during nitroprusside infusion may not be routinely required.     

The echocardiogram in left atrial myxoma

A case of left atrial myxoma is described in which the echocardiogram provided the clue to the diagnosis. The mechanisms involved in producing a positive result are discussed. The value of the echocardiogram appears to depend upon echoes from the tumor during diastole which can be detected immediately posterior to the anterior cusp of the mitral valve. In this case the tumor was successfully removed with restoration of the normal pattern of mitral valve movement.     

Total occlusion of the left main coronary artery. A clinical, hemodynamic and angiographic profile

Although left main coronary artery stenosis has been extensively revicwed, total occlusion of the left main coronary artery has received scant attention. Six patients were diagnosed at cardiac catheterization as having total occlusion of the left main coronary artery over a period of seven years at two institutions. They ranged in age from 32 to 72 years, and all had symptoms ranging from NYHA Class 1-IV at initial presentation. One patient died three days after coronary artery bypass graft surgery. Of the remaining five, two treated medically are alive four and 40 months after catheterization, and three treated with coronary artery bypass graft surgery are alive three, 66 and 68 months after catheterization. Electrocardiogram showed prior myocardial infarction in three patients, stress tests were positive in three of four patients, and hyperlipidemia was present in the five tested. In the three patients without prior myocardial infarction, left ventricular function was preserved (ejection fractions = 0.52, 0.55 and 0.64; left ventricular end-diastolic pressures = 6, 9 and 14 mm Hg). Injection of the right coronary artery in this group revealed extensive collaterals filling the left coronary artery. The three patients with prior myocardial infarction had impaired left ventricular function (ejection fractions = 0.18, 0.30 and 0.33; left ventricular end diastolic pressures = 26, 35 and 35 mm Hg) and sparse intercoronary collaterals. Patients with total occlusion of the left main coronary artery have a varying clinical presentation and may have prolonged survival. In patients with good collaterals, left ventricular function may be preserved.     

Morphologic, biochemical and physiologic alterations in a case of idiopathic hypoalbuminemia (analbuminemia).

A patient with idiopathic hypoalbuminemia is described. A study of albumin kinetics demonstrated slowed albumin degradation suggesting low albumin synthesis. Morphologic observation of hepatocellular alterations suggested decreased protein synthesis. The intra- and extravascular space was low with an abnormally large postural shift of intravascular fluid into the extravascular compartment. Disturbances in the concentration of plasma lipids and of several plasma proteins were detected. The effect of albumin infusion on these physiologic and biochemical abnormalities suggests that most occurred as a secondary response to the hypoalbuminemic state. Evaluation of the patient's kindred revealed no members with hypoalbuminemia.     

Diuretic-induced ventricular ectopic activity

The need to avoid hypokalemia during diuretic therapy in nondigitalized patients has been questioned. Twenty-one patients with (1) mild essential hypertension, (2) plasma potassium of < 3.5 meq/liter during previous diuretic treatment, and (3) normal findings {< 6 unifocal ventricular premature beats/hour} on 24-hour ambulatory electrocardiographic monitoring and exercise testing were treated with hydrochlorothiazide (50 mg twice a day) for four weeks and then ambulatory electrocardiographic monitoring and exercise testing were repeated. Ambulatory electrocardiographic monitoring revealed that ventricular ectopic activity developed in seven patients and complex ventricular ectopic activity (multifocal ventricular premature beats, ventricular couplets and/or ventricular tachycardia) in four. Only two of these seven had ventricular ectopic activity during exercise testing while they were hypokalemic. Potassium repletion in these seven patients with spironolactone abolished complex ventricular ectopic activity and reduced unifocal ventricular premature beats significantly (p < 0.01) from an average of 71.2 ventricular premature beats/hour/patient during hydrochlorothiazide treatment to 5.4 ventricular premature beats/hour/patient after potassium repletion. Although complex ventricular ectopic activity was more likely to occur with plasma potassium < 3.0 meq/ liter, restoration of normokalemia was required in several patients to abolish residual ventricular ectopic activity. Persistent ventricular ectopic activity in one patient suggested that myocardial injury sustained during hypokalemia may initiate chronic ventricular ectopic activity. Even in nondigitalized patients, the hazard of diuretic-induced ventricular ectopic activity warrants correction of hypokalemia.     

Sinus node dysfunction. An overview with emphasis on autonomic and pharmacologic consideration.

Sinus node dysfunction is a disorder of impulse generation and impulse conduction. Previous works have emphasized that the dysfunction occurs not only within the sinus node but also within the escape pacemaker. Adrenergic and cholinergic mechanisms, as well as pulsations and pressure within the sinus node artery, play an important role in normal sinus node activity. Although perinodal fibers act as a buffer zone for sinoatrial conduction, their role in man is yet to be clarified. During normal sinus node activity, pacemaker shifts from the sinus node to the crista terminalis have been shown to occur. Following sinus node destruction, similar shifts do occur. Clinical methods of determining sinus node function, such as the sinus node recovery time and sinus atrial conduction time, are useful but have limitations. Dynamic electrocardiographic monitoring provides the best clinical method available for detecting sinus node dysfunction. Digitalis appears to improve the parameters of sinus node function by increasing the automaticity of latent atrial pacemakers. The atrial arrhythmia of sinus node dysfunction appears to be related to the characteristics of latent atrial pacemaker and "enhanced" cholinergic tone.     

Multiple adenocarcinomas and premalignant changes in "backwash" ileitis.

In a patient with long-staning ulcerative colitis and "backwash" ileitis, multiple carcinomas developed in the colon and ileum. In both locations premalignant mucosal changes of the basal cell proliferation type were seen adjacent to and remote from sites of carcinoma. Although the frequency of such premalignant and malignant changes in "backwash" ileitis is unknown, their concurrence in this case suggests that ulcerative colitis involving the terminal ileum increases the risk of small bowel carcinoma.     

The assessment of immunologic and clinical changes occurring during corticosteroid therapy for allergic bronchopulmonary aspergillosis

Twenty-two patients with allergic bronchopulmonary aspergillosis have been treated and evaluated for a period ranging from two months to nine years. Twelve are available for periodic blood sampling. Data are presented suggesting the following: (1) Patients with allergic bronchopulmonary aspergillosis have high initial levels of total serum immunoglobulin E (IgE). These levels are significantly higher in those patients who had not been previously treated with prednisone for the control of asthma. (2) Treatment with alternate day prednisone (0.5 mg/kg given on alternate days) caused clinical and roentgenologic improvement as well as marked decreases in total serum IgE but does not necessarily prevent recurrence of the disease. (3) Total and specific IgE against Aspergillus antigen may increase prior to and during exacerbations of disease. (4) Specific IgG and IgE against Aspergillus antigen are increased in most patients with allergic bronchopulmonary aspergillosis and reflect disease activity as evidenced by x-ray and clinical exacerbations in some cases. (5) Lymphocyte transformation using Aspergillis antigen, as measured by the whole blood technic, is present in patients with allergic bronchopulmonary aspergillosis, but serial changes in lymphocyte transformation do not correlate with disease activity. (6) Precipitin reactions are present in patients with allergic bronchopulmonary aspergillosis, but presence or absence does not reflect disease activity in most cases.     

Immunologic events preceding clinical exacerbation of systemic lupus erythematosus

A patient with diffuse glomerulonephritis due to systemic lupus erythematosus is described. Serial urinalyses and special immunologic determinations were performed as he responded to treatment of his first attack of systemic lupus erythematosus. The sequence of immunologic events preceding the onset of his second attack of lupus nephritis are recorded. Falling levels of total serum complement (CH₅₀) and of the first component of complement (C1q), rising levels of antibody to double and single stranded deoxyribonucleic acid (DNA) and finally circulating protein complexes that precipitate C1q in vitro developed months before clinical evidence of exacerbation of his extra renal or renal disease. Abnormalities of L-chain protein metabolism provided a particularly early guide to exacerbation of the disease. The use of this group of laboratory determinations to anticipate exacerbations of the disease and to guide therapy is discussed.     

The therapeutic approach to hypoparathyroidism

Hypoparathyroid patients have for decades been subjected to vitamin D therapy, in varying pharmacologic doses, with widely discrepant responses. They have been hypocalcemic on extremely large doses of the vitamin and hypercalcemic on doses that are not toxic to normal persons. The resistance to conventional forms of vitamin D and calcium supplementation therapy has produced a need for other therapeutic preparations. Dihydrotachysterol (DHT), 25-(OH)D₃ and 1α-(OH)D have been tried in short-term studies, often with limited success. More detailed analyses of long-term results of therapy with 25-(OH)D, 1,25-(OH)₂D or 1α-(OH)D are warranted before their superiority over vitamin D and DHT therapy can be established. Until such time that these substances are available in sufficient quantities for these studies, a rational approach to vitamin D therapy should include a more definitive analysis of the factors leading to the hypocalcemic hyperphosphatemic state. This knowledge should be combined with an appreciation of the effects of emotion and psychologic stress, estrogens, oral contraceptives, tranquilizers, anticonvulsants, magnesium deficiency, dietary indiscretions and diuretics on calcium homeostasis. Measurements of circulating PTH levels and para-thyroid reserve, and reservations about accepting urinary values as estimates of circulating calcium levels in treated patients would add additional sophistication to planned therapeutic approaches with vitamin D. The final result of these combined endeavors may ultimately lead to better control and a much happier patient.     

Immunoglobulin and autoantibody response in acute and chronic liver disease

Serum immunoglobulin and nonorgan-specific autoimmune responses (autoantibody response) were studied in 269 patients with a variety of acute and chronic liver disease. A majority of patients with hepatitis B antigen (HB Ag)-positive and HB Agnegative acute viral hepatitis showed a mild elevation in total globulin, gamma globulin, immunoglobulin G (IgG) levels and a moderate elevation in immunoglobulin M (IgM) levels during the first 2 weeks of illness; these levels began to subside by the 8th week of illness and were completely normal by the 12th week, concomitant with the return of normal transaminase values. Serum complement (C₃) levels were low in 20 per cent of the patients with acute viral hepatitis, during the first 2 weeks of illness and returned to normal thereafter. Of the 80 patients with acute viral hepatitis, 42.5 per cent had smooth muscle antibody (SMA), 20.5 per cent had mitochondrial antibody (MA), 10 per cent had rheumatoid factor (RA), and none had antinuclear antibody (ANA); these nonorgan-specific autoimmune markers were only transiently present (mean, 2 weeks) and became undetectable as the patient's condition improved. There was no difference in these immunologic responses between patients with HB Ag-positive and HB Ag-negative acute viral hepatitis. High levels of gamma globulin and IgG were seen in chronic active liver disease, either of viral or alcoholic etiology. Serum immunoglobulin A (IgA) levels were elevated only in those with alcoholic liver disease, whereas IgM levels were high in those with liver disease associated with an active hepatocellular damage either of alcoholic or viral etiology. HB Ag-positive blood donors with asymptomatic mild liver disease had normal immunochemistry values.     

Resting U wave inversion as a marker of stenosis of the left anterior descending coronary artery

Resting 12-lead electrocardiographic records from 849 patients who underwent coronary cineangiographic studies were reviewed for U wave negativity without knowledge of the clinical data or angiographic results. In order to evaluate U wave negativity as an independent electrocardiographic sign, patients with significant Q waves in the anterior leads were excluded from the final data analysis leaving 760 patients. Twenty-seven patients had U wave negativity in leads I, a VL or V₄ through V₆. For the study population, the prevalence of coronary artery disease was 64 percent (484 of 760); the prevalence of significant left anterior descending or left main coronary artery stenosis was 46 percent (350 of 760); and the prevalence of angiographic left ventricular dysfunction was 41 percent (309 of 754). Among 27 patients with resting U wave negativity the prevalence of coronary artery disease was 89 percent (24 of 27); the prevalence of left anterior descending or left main disease was 89 percent (24 of 27); and the prevalence of angiographic left ventricular dysfunction was 80 percent (20 of 25). Among patients selected for coronary cineangiographic study, U wave negativity was a significant predictor (p <0.001) of ?75 percent stenosis of the left anterior descending or left main coronary artery and of left ventricular dysfunction (p <0.001).     

Comparison of the effects of sleep, exercise and autonomic drugs on ventricular extrasystoles, using ambulatory monitoring of electrocardiogram and electroencephalogram.

Ambulatory monitoring of the electrocardiogram (ECG) and the electroencephalogram (EEG) in 12 untreated patients with frequent ventricular extrasystoles showed a significant decrease in both ventricular extrasystoles and heart rate during sleep. The decrease in ventricular extrasystoles correlated more closely with the change in heart rate than with the level of arousal. During wakefulness, similar changes in ventricular extrasystoles and heart rate could be produced by the intravenous administration of propranolol and, to a lesser extent, by phenylephrine. Exercise produced an initial increase in ventricular extrasystoles, with suppression at higher levels in most patients. Thus, the frequency of ventricular extrasystoles is usually reduced at both extremes of heart rate, and the changes that occur during sleep can be explained by autonomic mediation, with the sympathetic limb of the autonomic nervous system having a greater effect than the vagus.     

Complications and consequences of endotracheal intubation and tracheotomy: A prospective study of 150 critically ill adult patients

A prospective study of the complications and consequences of translaryngeal endotracheal intubation and tracheotomy was conducted on 150 critically ill adult patients. Adverse consequences occurred in 62 percent of all endotracheal intubations and in 66 percent of all tracheotomies during placement and use of the artificial airways. The most frequent problems during endotracheal intubation were excessive cuff pressure requirements (19 percent), self-extubation (13 percent) and inability to seal the airway (11 percent). Patient discomfort and difficulty in suctioning tracheobronchial secretions were very uncommon. Problems with tracheotomy included stomal infection (36 percent), stomal hemorrhage (36 percent), excessive cuff pressure requirements (23 percent) and subcutaneous emphysema or pneumomediastinum (13 percent). Complications of tracheotomy were judged to be more severe than those of endotracheal intubation. Follow-up studies of survivors revealed a high prevalence of tracheal stenosis after tracheotomy (65 percent) and significantly less after endotracheal intubation (19 percent) (p < 0.01). Thirty-nine of 41 (95 percent) patients with endotracheal intubation and 20 of 22 (91 percent) patients with tracheotomy had laryngotracheal injury at autopsy. Ulcers on the posterior aspect of the true vocal cords were found at autopsy in 51 percent of the patients who died after endotracheal intubation. There was no significant relationship between the duration of endotracheal intubation or tracheotomy and the over-all amount of laryngotracheal injury at autopsy, although patients with prolonged endotracheal intubation followed by tracheotomy had more laryngeal injury at autopsy (P = 0.06) and more frequent tracheal stenosis (P = 0.05) than patients with short-term endotracheal intubation followed by tracheotomy. Adverse effects of both endotracheal intubation and tracheotomy are common. The value of tracheotomy when an artificial airway is required for periods as long as three weeks is not supported by data obtained in this study.     

The effect of isosorbide dinitrate on left ventricular size,wall stress and left ventricular function in chronic refractory heart failure: An echocardiographic study

To determine the effect of a long-acting vasodilator isosorbide dinitrate (ID) on ventricular performance, 16 patients with refractory congestive heart failure underwent echocardiographic studies during control and for a period of 2 hours after the administration of 10 mg of sublingual ID. The effects of ID were seen in 5 to 10 minutes, reached maximum at 30 ± 3 minutes lasted for 60 minutes and dissipated thereafter. At the maximal drug effect, a significant decline in mean blood pressure (74 ± 2 versus 81 ± 3 mm Hg, p < 0.001), left ventricular afterload (228 × 10³ ± 9 × 10³ dynes/cm² versus 273 × 10³ ± 12 × 10³ dynes/cm² p < 0.001), end-diastolic dimension (5.90 ± 0.13 versus 6.40 ± 0.15 cm, p < 0.005) and end-systolic dimension (4.8 ± 0.15 versus 5.50 ± 0.17 cm, p < 0.001) occurred. These changes were associated with a significant increase in per cent fractional shortening (19 ± 2 per cent versus 14.5 ± 1.3 per cent, p < 0.001), mean rate of circumferential fiber shortening (VCF) (0.78 ± 0.06 versus 0.61 ± 0.05 circumferences per second (circ/sec) p < 0.001) and normalized mean posterior wall velocity (VPW) (0.65 ± 0.05 versus 0.47 ± 0.03 sec^?1, p < 0.001) when heart rate was not significantly altered. All 16 patients were maintained on long-term ID therapy. Six of 16 patients (38 per cent) died within 17 to 270 days after the acute study. Nine of 16 patients have been followed for a period of three to 24 months and are clinically improved. These findings suggest that (1) ID reduces left ventricular size, preload and afterload, and improves ventricular performance; and (2) the use of ID might be of value as adjunctive therapy in acute/chronic management of refractory heart failure.     

The value of the electrocardiogram in the differential diagnosis of a tachycardia with a widened QRS complex

To determine the value of the electrocardiogram for differentiating aberrant conduction from ventricular ectopy, findings were retrospectively reviewed from patients with a widened QRS complex during tachycardia in whom the site of origin of tachycardia was determined by His bundle electrography. Seventy episodes of sustained ventricular tachycardia from 62 patients and 70 episodes of aberrant conduction during supraventricular tachycardia from 60 patients were available for study. Findings suggesting a ventricular origin of tachycardia were (1) QRS width over 0.14 sec, (2) left axis deviation, (3) certain configurational characteristics of QRS and (4) atrioventricular (A-V) dissociation. Capture or fusion beats resulting from A-V conduction of dissociated atrial complexes during ventricular tachycardia were seen during only four of 33 episodes of sustained tachycardia.