Osteitis deformans (Paget's disease) and calcific disease of the heart valves.

The prevalence of calcific aortic valve stenosis in Paget's disease (osteitis deformans) was investigated by reviewing autopsy data of severe cases (> or = 75% involvement of > or = 3 major bones, the femur, tibia, skull, and pelvis) and moderate cases (> or = 75% involvement of only 1 or 2 major bones) of Paget's disease. Comparisons were made with normal age-matched controls. Aortic stenosis (AS) was present in 24% of 27 autopsies of severe Paget's disease compared with 3.5% in 201 controls (p <0.01). Clinical signs of AS were present in 39% of 102 patients with severe Paget's disease compared with 4% in 417 controls (p <0.101). The prevalence of AS in 18 cases of moderate Paget's disease was similar to that of controls. Electrocardiograms were reviewed in 45 cases of Paget's disease and compared with 80 controls of similar age. Complete atrioventricular (AV) block, incomplete AV block, bundle branch block, and left ventricular hypertrophy were present in 11%, 11%, 20%, and 13% of the Paget's cases and in only 2.5%, 1.3%, 2.5%, and 3.8% in the control cases (p <0.05, <0.05, <0.01, and <0.05, respectively). It is concluded that in severe Paget's disease there is a high prevalence of AS, heart block, and bundle branch block, but these are not present in moderate degrees of bone involvement.

High altitude pulmonary edema: hemodynamic aspects.

Over 30 years ago hemodynamic studies on patients with high altitude pulmonary edema (HAPE) excluded the prior contention that the basic cause was left ventricular failure and correctly implicated the pulmonary circulation as the culprit. Physiological studies during the acute stage have revealed a normal pulmonary artery wedge pressure, marked elevation of pulmonary artery pressure, severe arterial unsaturation, and usually a low cardiac output. Pulmonary arteriolar (pre-capillary) resistance was elevated. A working hypothesis of the etiology of HAPE suggests that hypoxic pulmonary vasoconstriction is extensive but not uniform. The result is overperfusion of the remaining patent vessels with transmission of the high pulmonary artery pressure to capillaries. Dilatation of the capillaries and high flow results in capillary injury with leakage of protein and red cells into the alveoli. While hypoxic vasoconstriction appears to be the major cause of patchy vascular obstruction the occurrence of thrombi in the pulmonary vessels may also play a role in more severe and advanced cases. The above concept of the mechanism of HAPE has been further supported by animal studies showing pulmonary edema occurring when increased pressure and flow is produced in a portion of the pulmonary vascular bed. Clinical studies which have supported this concept include the susceptibility to HAPE of patients with an absent pulmonary artery, pulmonary edema occurring in pulmonary embolism, following removal of pulmonary arterial thrombi and following balloon dilatation of stenoses of branches of the pulmonary artery. In addition to those hemodynamic factors an increase in capillary permeability due to cell derived products resulting from capillary wall injury is an important aspect of edema formation.

Lung pathology in high-altitude pulmonary edema.

Autopsy findings in 10 cases of high-altitude pulmonary edema have been collected from published articles and personal observations. All cases were males with a mean age of 37 years (22-62). The altitude of occurrence was from 8400 to 17 500 feet. The mean combined lung weight in nine cases was 1682 g (1200-3000 g). Cerebral edema was present in five of eight cases. The most frequency pulmonary findings in addition to diffuse edema consisted of leukocyte infiltrates, alveolar hemorrhages, thrombi in small pulmonary arteries, and alveolar hyaline membranes. Pulmonary infarction was present in only one case. Right ventricular dilatation was commonly present. The left ventricle was normal. No significant coronary disease was present.

High-altitude pulmonary edema at a ski resort.

Medical records of 150 patients with high-altitude pulmonary edema seen over a 39-month period in a Colorado Rocky Mountain ski area at 2,928 m (9,600 ft) (mean age 34.4 years; 84% male) were reviewed. The mean time to the onset of symptoms was 3 +/- 1.3 days after arrival. Common symptoms were dyspnea, cough, headache, chest congestion, nausea, fever, and weakness. Orthopnea, hemoptysis, and vomiting were rare, occurring in 7%, 6%, and 16%, respectively. Symptoms of cerebral edema occurred in 14%. A temperature exceeding 100 degrees F occurred in 20%, and 17% had a systolic blood pressure of 150 mm of mercury or higher. Blood pressures were higher in patients older than 50 years (142 mm of mercury). Rales were present in 85%, and a pulmonary infiltrate was present in 88%; both were most commonly bilateral or on the right side. The amount of infiltrate was mild. Men appeared to be more susceptible than women to high-altitude pulmonary edema. Pulse oximetry in 45 patients showed a mean oxygen saturation of 74% (38% to 93%). Treatment methods depended on severity and included a return to quarters for portable nasal oxygen, an overnight stay in the clinic for continuing oxygen, or a descent to Denver for recovery or admission to a hospital. All patients received oxygen for 2 to 4 hours in the clinic. There were no deaths or complications.

High-altitude pulmonary edema: current concepts.

High-altitude pulmonary edema (HAPE) occurs in unacclimatized individuals who are rapidly exposed to altitudes in excess of 2450 m. It is commonly seen in climbers and skiers who ascend to high altitude without previous acclimatization. Initial symptoms of dyspnea, cough, weakness, and chest tightness appear, usually within 1-3 days after arrival. Common physical signs are tachypnea, tachycardia, rales, and cyanosis. Descent to a lower altitude, nifedipine, and oxygen administration result in rapid clinical improvement. Physiologic studies during the acute stage have revealed a normal pulmonary artery wedge pressure, marked elevation of pulmonary artery pressure, severe arterial unsaturation, and usually a low cardiac output. Pulmonary arteriolar (precapillary) resistance is elevated. A working hypothesis of the etiology of HAPE suggests that hypoxic pulmonary vasoconstriction is extensive but not uniform. The result is overperfusion of the remaining patent vessels with transmission of the high pulmonary artery pressure to capillaries. Dilatation of the capillaries and high flow results in capillary injury, with leakage of protein and red cells into the alveoli and airways. HAPE represents one of the few varieties of pulmonary edema where left ventricular filling pressure is normal.

How well do older persons tolerate moderate altitude?

We studied the physiologic and clinical responses to moderate altitude in 97 older men and women (aged 59 to 83 years) over 5 days in Vail, Colorado, at an elevation of 2,500 m (8,200 ft). The incidence of acute mountain sickness was 16%, which is slightly lower than that reported for younger persons. The occurrence of symptoms of acute mountain sickness did not parallel arterial oxygen saturation or spirometric or blood pressure measurements. Chronic diseases were present in percentages typical for ambulatory elderly persons: 19 (20%) had coronary artery disease, 33 (34%) had hypertension, and 9 (9%) had lung disease. Despite this, no adverse signs or symptoms occurred in our subjects during their stay at this altitude. Our findings suggest that persons with preexisting, generally asymptomatic, cardiovascular or pulmonary disease can safely visit moderate altitudes.

Oxygen transport and cardiovascular function at extreme altitude: lessons from Operation Everest II.

Operation Everest II was designed to examine the physiological responses to gradual decompression simulating an ascent of Mt Everest (8,848 m) to an inspired PO2 of 43 mmHg. The principal studies conducted were cardiovascular, respiratory, muscular-skeletal and metabolic responses to exercise. Eight healthy males aged 21-31 years began the "ascent" and six successfully reached the "summit", where their resting arterial blood gases were PO2 = 30 mmHg and PCO2 = 11 mmHg, pH = 7.56. Their maximal oxygen uptake decreased from 3.98 +/- 0.2 L/min at sea level to 1.17 +/- 0.08 L/min at PIO2 43 mmHg. The principal factors responsible for oxygen transport from the atmosphere to tissues were (1) Alveolar ventilation--a four fold increase. (2) Diffusion from the alveolus to end capillary blood--unchanged. (3) Cardiac function (assessed by hemodynamics, echocardiography and electrocardiography)--normal--although maximum cardiac output and heart rate were reduced. (4) Oxygen extraction--maximal with PvO2 14.8 +/- 1 mmHg. With increasing altitude maximal blood and muscle lactate progressively declined although at any submaximal intensity blood and muscle lactate was higher at higher altitudes.

Quality of life after bypass surgery for unstable angina. 5-year follow-up results of a Veterans Affairs Cooperative Study.

To assess the effect of bypass surgery on outcome from unstable angina, 468 patients were randomized to medical treatment (237 patients) or surgery plus medical treatment (231 patients) and have been followed for comparison of survival, cardiac end points, and quality of life; the latter end point is discussed in the present report. Data were available at 3 and 5 years for 80% and 82% of patients in the medical group, respectively, and 77% and 80% of patients in the surgery group, respectively. At 3 months after randomization to therapy, 79.8% of patients in the surgery group reported subjective improvement, compared with 58% of the medical group, 12.6% of the surgery group reported no change compared with 24.5% of the medical group, and 5.5% of the surgery group reported worsening compared with 24.5% of the medical group (p less than 0.01 by chi 2). Similar data were found for chest pain status, and the benefit to the surgery group remained statistically significant through 5 years of follow-up. Crossover rate to surgery was 43% by 5 years. Treadmill duration was increased in the surgery group compared with the medical group (6.5 +/- 0.25 versus 5.3 +/- 0.25 minutes at 6 months, p less than 0.01), and a significant difference was again demonstrated at 3 and 5 years. A trend toward decreased recurrence of unstable angina was present in the surgery group at 1 year (six of 168 [3.6%] versus 13 of 187 [6.9%] in the medical group, p = 0.158), but the two groups were similar at 3 and 5 years.(ABSTRACT TRUNCATED AT 250 WORDS)

Diagnostic accuracy of continuous wave Doppler echocardiography in severe aortic stenosis in the elderly.

Forty-four male patients (mean age 63.6 years) with aortic stenosis (AS) were evaluated by conventional hemodynamic methods and continuous wave (CW) Doppler echocardiography. The relationship between Doppler mean gradients and direct mean pressure gradients in all patients was significant, with an r value of 0.88. Sixteen of 17 patients with a mean Doppler gradient greater than or equal to 40 mmHg had severe AS (AVA less than or equal to 1.0 cm2). Twenty-seven patients had a Doppler gradient less than 40 mmHg, and 8 of these patients had severe AS (AVA less than or equal to 1.0 cm2). The sensitivity and specificity of a Doppler gradient greater than or equal to 40 mmHg in detecting severe AS were, therefore, 67% and 95%, respectively. Thirty-three percent (8/24) of patients with severe AS and low Doppler gradients (less than 40 mmHg) had evidence of poor left ventricular function, evidenced by a lower cardiac output, a higher heart rate and an abnormal PEP/LVET ratio compared to the other patients. Thus, the presence of a low stroke volume less than or equal to 60 ml/beat and PEP/LVET x HR greater than 26 is of value in identifying patients where the Doppler is likely to significantly underestimate the degree of aortic stenosis.

Prevalence and characteristics of the aortic ejection sound in adults.

A survey of 1,950 phonocardiograms recorded over a 6-year period revealed 170 (9%) with a distinct aortic ejection sound. All patients were men with a mean age of 61 years (range 29 to 88). Associated clinical features were: aortic stenosis in 28%, history of systemic hypertension in 10%, history of rheumatic fever in 4% and none of these features in 58% of patients. In 141 (83%) of 170 patients the aortic ejection sound occurred simultaneously with or 0.01 second before or after the onset of the rise of the externally recorded carotid pulse. In 37 (66%) of 56 patients who had simultaneous echocardiograms and phonocardiograms recorded, the aortic ejection sound occurred at 0.01 second before or after the maximal opening point of the aortic valve leaflets. Two-dimensional echocardiography was performed in all patients and a bicuspid aortic valve was identified in 38 patients (22%). In 83 patients (49%) 3 cusps were clearly seen. In 49 patients (29%) an accurate determination was not possible. Anatomic examination of 120 consecutive aortic valves at autopsy was performed to identify possible causes of the aortic ejection sound. In 18 (15%) of autopsies fusion of 2 aortic cusps extending greater than or equal to 5 mm from the attachment to the aorta was observed. This abnormality, aortic commissural fusion, may be congenital or acquired. It is concluded that aortic ejection sounds may occur in patients without bicuspid aortic valves and in a variety of clinical conditions. A moderate degree of cuspal fusion may be the cause of the sound.

Progression of aortic stenosis in adult men. Detection by noninvasive methods.

One hundred seventy-one patients with aortic stenosis (AS) who had hemodynamic studies were evaluated by a scoring system of the seven following noninvasive variables which our laboratory had developed to estimate the severity of AS: left ventricular hypertrophy (LVH) by ECG; visible aortic valve calcification by chest x-ray examination; loudness of A2; Q to peak of systolic murmur; T-time of the carotid pulse; LV ejection time; and LVH by M-mode echocardiography. The range of the severity score is 0 to 16, and a score greater than or equal to 5 has been shown correctly to identify 93 percent of patients with severe AS (valve area less than or equal to 1.0 cm2). The present study has applied this method to the detection of progression of AS. Eleven patients (mean age, 60.4 years) were studied who had hemodynamic studies performed two to nine years apart (mean, three years). Progression of stenosis occurred in all, with an increase in mean aortic valve gradient from 23 +/- 4.7 mm Hg to 46 +/- 6.5 mm Hg (p less than 0.005). Aortic valve area decreased from 1.5 +/- 0.18 cm2 to 0.88 +/- 0.10 cm2 (p less than 0.005). Noninvasive scores increased in these patients from 0.7 +/- 0.5 to 7.1 +/- 2.3 (p less than 0.005). Thirty-five patients (mean age, 62.4 years) had repeat noninvasive studies one to six years apart (mean 3 years). Twenty-two (63 percent) had an increase in the noninvasive score of greater than or equal to 3 points, and 20 (57 percent) attained a score of greater than or equal to 5, indicating probable severe AS. The mean initial severity score was 2.2 +/- 0.3, and at the end of a mean follow-up of three years, the score was 8.3 +/- 0.6 (p less than 0.005). It is concluded that in the elderly male, progression of AS over a three-year period occurs in about 60 percent of patients, and progression can be detected by simple, noninvasive methods.

Noninvasive evaluation of the severity of aortic stenosis in adults.

A noninvasive point score system for the evaluation of severity of aortic stenosis (AS) was employed in a prospective study of 153 patients (mean age 64.8 +/- 0.8 years) referred from invasive studies or for the evaluation of a systolic murmur. Seven variables were recorded and scored as follows: LVH by ECG (0-2); aortic valve calcium by chest x-ray film (0-2); loudness of A2 (0-2); Q-peak of murmur (0-3); T-time of carotid pulse (0-3); ejection time (0-3); and LVH by echo (0-1). Range of the total score was 0-16. All patients had the aortic valve area (AVA) determined by cardiac catheterization. Data analysis revealed that the relation between the total score and the AVA was curvilinear with a score greater than or equal to 5 correctly identifying 100/107 (93 percent) of patients with a valve area of less than or equal to 1.0 cm2. If the patients with an AVA of less than or equal to 1.0 cm2 were considered severe and patients with a total score less than 5 were considered mild-moderate, the sensitivity, specificity, and predictive accuracy for a score greater than or equal to 5 were 93 percent, 96 percent, and 98 percent, respectively. The relation between the score and aortic valve gradient (AVG) was linear with a score of greater than or equal to 5 correctly identifying 84/88 (95 percent) with an AVG greater than or equal to 40 mm Hg. If the patients with a pressure gradient over 40 mm Hg were considered severe, the sensitivity, specificity, and predictive accuracy for a score greater than or equal to 5 were 95 percent, 72 percent, and 82 percent, respectively. It is concluded that a point score system employing seven noninvasive variables is simple and accurate in identifying patients with severe AS and would be a valuable addition to a Doppler determined gradient.

Exercise tests and ventricular tachycardia.

All treadmill exercise tests done at the Palo Alto Veterans Administration Medical Center from 1973 to 1982 were reviewed to identify episodes of ventricular tachycardia (>/=3 consecutive ventricular ectopic complexes) or ventricular fibrillation occurring during or within 8 minutes of cessation of symptom-limited exercise. Of patients with a clinical diagnosis of coronary artery disease (900 tests), ventricular tachycardia occurred in 36 (4.0%) and ventricular fibrillation in 6 (0.7%). Of patients without known coronary disease (1,700 tests), ventricular tachycardia occurred in 12 (0.07%), and no patient had ventricular fibrillation. Most arrhythmias ceased spontaneously and only 5 patients required cardioversion. We conclude that exercise tests are safe, the incidence of ventricular tachycardia or ventricular fibrillation is low-these arrhythmias occurring largely in patients with known coronary disease-spontaneous return to sinus rhythm is common and no deaths were associated with 2,400 consecutive tests.

The 5 year effect of bypass surgery on relief of angina and exercise performance.

The 5 year effect of medical vs surgical treatment on symptoms and exercise performance was evaluated in patients with stable angina who entered the Veterans Administration Cooperative Study from 1972 to 1974. Severity of angina was evaluated by a physician-administered angina questionnaire and physical working capacity was assessed by exercise testing. Angina was substantially relieved in surgical patients at 1 year, with 78% having mild or no angina compared with only 28% at entry. The corresponding rates in medical patients showed little change: 38% at 1 year and 32% at entry. At 5 years the percentage of surgical patients with mild or absent angina decreased from the 1 year rate of 78% to 64%, whereas the medical group exhibited a small increase from 38% to 49%. Similar results were obtained by evaluating changes in angina compared to entry. At 1 year 49% of surgical patients were markedly improved compared with only 12% of medical patients. At 5 years the percentage of surgical patients who remained markedly improved decreased to 41%, whereas the medical group with marked improvement increased slightly from 12% at 1 year to 17% at 5 years. Medication requirements were markedly reduced in surgical patients with only a slight increase in medical patients. Exclusion of nonadherers from the analysis did not change the results. Exercise testing revealed comparable changes in physical performance. At 1 year surgical patients had fewer tests stopped by angina compared with medical patients (28% vs 64%), a higher estimated oxygen consumption (26 vs 21 ml/kg/min) and treadmill exercise duration (7.3 vs 4.9 min). Other measures of exercise performance were comparably improved.(ABSTRACT TRUNCATED AT 250 WORDS)