Kevin M. McIntyre

The Hemodynamic Response to Pulmonary Embolism in Patients Without Prior Cardiopulmonary Disease

The hemodynamic status of 20 patients free of prior cardiopulmonary disease was related to the degree of pulmonary embolic obstruction estimated by selective pulmonary angiography. Angiographic estimation of obstruction ranged from 13 to 68 percent. Systemic arterial hypoxemia occurred in virtually all patients (95 percent) including those with only 13 percent obstruction, thus suggesting that angiographically detectable emboli virtually do not occur without producing systemic hypoxemia. Mean pulmonary arterial pressure was increased in 14 patients (70 percent) and was consistently increased when obstruction exceeded 30 percent. Elevation of the level of mean right atrial pressure was found in 10 patients (50 percent) and was usually associated with obstruction in excess of 35 percent and mean pulmonary arterial pressure in excess of 30 mm Hg. Good correlation was observed between mean pulmonary arterial pressure and angiographic estimation of obstruction (P < 0.01), mean right atrial pressure and obstruction (P < 0.01), mean pulmonary and right atrial pressures (P < 0.01), and pO2 and obstruction (P < 0.05). Cardiac index was characteristically normal or mildly increased, being below the lower limit of normal in only 4 patients (20 percent). In patients who had not experienced cardiac failure, the cardiac index appeared to increase as systemic arterial pO2 decreased (P < 0.01) once hypoxemia was well established. Mean pulmonary arterial pressure never exceeded 40 mm Hg, despite massive obstruction in some patients, thereby suggesting that this level approximates the maximal pressure response of the previously normal right ventricle.

Relation of neurohumoral activation to clinical variables and degree of ventricular dysfunction: A report from the registry of studies of left ventricular dysfunction☆

OBJECTIVES This study examined the relation between neurohumoral activation and severity of left ventricular dysfunction and congestive heart failure in a broad group of patients with depressed left ventricular function who were not recruited on the basis of eligibility for a therapeutic trial. BACKGROUND Previous studies have established the presence of neurohumoral activation in patients with severe congestive heart failure. It is not known whether the activation of these neurohumoral mechanisms is related to an impairment in left ventricular function. METHODS From the 6,273 patients recruited into the Studies of Left Ventricular Dysfunction Registry (SOLVD), a subgroup of 859 patients were randomly selected, and their plasma norepinephrine, plasma renin activity, arginine vasopressin and atrial natriuretic peptide levels were correlated with clinical findings, New York Heart Association functional class, left ventricular ejection fraction and drug use. RESULTS There was a weak but significant correlation between ejection fraction and an increase in plasma norepinephrine (rho = -0.18, p < 0.0001), plasma renin activity (rho = -0.24, p < 0.0001) and arginine vasopressin (rho = -0.12, p < 0.003). The only exception was atrial natriuretic peptide, which showed the best correlation to ejection fraction (rho = -0.37, p < 0.0001). Deterioration in functional class was associated more with increases in atrial natriuretic peptide (p = 0.0003) and plasma renin activity (p = 0.0003) and less with an increase in plasma norepinephrine. Of the clinical variables, elevated jugular venous pressure and third heart sound (S3) gallop were significantly associated with increased levels of plasma norepinephrine, plasma renin activity and atrial natriuretic peptide. We then compared the relation of neurohormones with clinical signs, functional status, ejection fraction and drug therapy and controlled for mutual interactive effects. After adjustment, a decrease in ejection fraction was still significantly related to an increase in plasma norepinephrine, plasma renin activity and atrial natriuretic peptide. In contrast, only a difference between functional classes I and III/IV was associated with an increase in plasma renin activity and atrial natriuretic peptide levels. CONCLUSIONS Neurohumoral activation in patients with heart failure is related to severity of left ventricular functional depression, and this relation is independent of functional class or concomitant drug therapy.

The electrocardiogram in acute pulmonary embolism

Electrocardiograms of 90 patients with arteriographically documented acute submassive or massive pulmonary embolism and no associated cardiac or pulmonary disease were studied. Patients were derived from the Urokinase-Pulmonary Embolism Trial National Cooperative Study. In massive embolism, the electrocardiogram was normal in 6 per cent (3 of 50) of patients. With submassive embolism, 23 per cent of patients (9 of 40) had a normal electrocardiogram. Since one or more of the traditional manifestations of acute cor pulmonale (S1Q3T3, right bundle branch block, P pulmonale, or right axis deviation) occurred in only 26 per cent of patients, one could not rely exclusively upon these electrocardiographic abnormalities for the diagnosis of pulmonary embolism. The most common electrocardiographic abnormalities were nonspecific T wave changes which occurred in 42 per cent of patients and nonspecific abnormalities (elevation or depression) of the RST segment which occurred in 41 per cent of patients. Left axis deviation occurring in 7 per cent of the patients was as frequent as right axis deviation. Low voltage QRS complexes, previously undescribed in pulmonary embolism, occurred in 6 per cent of patients. None of the patients had atrial flutter or atrial fibrillation, which appears to occur more typically in patients with pulmonary embolism who have preexistent cardiac disease. All of the varieties of electrocardiographic abnormalities disappeared in some of the patients by 2 wk. Inversion of the T wave was the most persistent abnormality. Larger defects on the lung scan or pulmonary arteriogram occurred in patients with various abnormalities on the electrocardiogram than in patients with normal electrocardiograms. The pulmonary arterial mean pressure and/or right ventricular end-diastolic pressure was significantly higher in patients with several varieties of abnormal electrocardiograms, although the partial pressure of oxygen in arterial blood, in general, did not differ from that in patients with normal electrocardiograms. These hemodynamic correlations, made for the first time in patients, suggest that acute ventricular dilatation, possibly in combination with hypoxemia, is a causative factor of the electrocardiographic changes in acute massive or submassive pulmonary embolism.

Assessment of quality of life as observed from the baseline data of the Studies of Left Ventricular Dysfunction (SOLVD) trial quality-of-life substudy

The improvement of aspects of a patients quality of life may be as important as prolonging survival in evaluating clinical trials of heart failure. The purpose of this study was to analyze the psychometric properties of the baseline measures from the quality-of-life substudy from the Studies of Left Ventricular Dysfunction (SOLVD) trial. The measures included the 6-Minute Walk Test, Dyspnea Scale, Living with Heart Failure, Physical Limitations, Psychologic Distress and Health Perceptions, as reported by both patients and staff. Cognitive functioning, such as Vocabulary, Digit Span and Trails Making, was also assessed. Patients were classified as New York Heart Association class I (n = 158) versus II or III (n = 150). The internal consistencies (i.e., reliabilities) of the self-report measures were high, except for the Health Perceptions of Class II or III patients. Reliability of the SOLVD quality-of-life battery was confirmed by significantly better life quality among New York Heart Association class I patients versus class II or III patients combined on the Walk Test, Physical Limitations, Dyspnea, Living with Heart Failure, Psychologic Distress and staff perceptions of patient health. In accordance with prior studies, the measures were uncorrelated with left ventricular ejection fraction. By demonstrating strong internal consistencies, reliability based on physician reports, and independence of ejection fraction levels, use of this quality-of-life assessment battery in this and other clinical trials of compromised ventricular functioning is supported.

Evaluation of Simulated Presence: a personalized approach to enhance well-being in persons with Alzheimer's disease.

OBJECTIVE: To evaluate the efficacy of Simulated Presence, a personalized approach to enhance well‐being among nursing home residents with Alzheimers disease and related dementias (ADRD).

Safety and efficacy of diltiazem hydrochloride for the treatment of stable angina pectoris: Report of a cooperative clinical trial

Sixty-three patients completed a multicenter 10 week, double-blind, parallel group protocol evaluating the efficacy of diltiazem versus placebo with respect to rate of attacks of angina, nitroglycerin consumption and duration of treadmill exercise. An additional 36 patients were evaluated for drug safety. A 4 week placebo lead-in phase was followed by a 2 week dose titration period and two treatment evaluation periods of 2 weeks each. Both diltiazem and placebo were associated with a significant reduction in weekly frequency of angina from the baseline rate. Intergroup comparison disclosed a significantly greater reduction for the patients receiving diltiazem than for those receiving placebo. A similar reduction was noted for nitroglycerin consumption. Total exercise duration at week 10 was statistically greater in patients treated with diltiazem. Diltiazem was well tolerated. No abnormalities in hematologic profiles or in routine serum chemistry values were observed; electrocardiographic P-R and QRS intervals were unaffected. Adverse effects that could have been related to drug administration were reported in 11 patients who received diltiazem and in 12 patients who received placebo. Of the 17 episodes in the diltiazem group only 3 were considered significant and drug-related, and only one of these resulted in discontinuation of the drug.

Long-term benefit of thrombolytic therapy in patients with pulmonary embolism

A total of 23 of the 40 patients who had angiographically proven pulmonary embolism and who had initially been randomized to an IV infusion of heparin (n = 11) or a thrombolytic agent (urokinase or streptokinase, n = 12) were restudied after a mean follow-up of 7.4 years to measure the right-sided pressures and to evaluate their response to exercise during supine bicycle ergometry. Results showed that, at rest, the pulmonary artery (PA) mean pressure and the pulmonary vascular resistance (PVR) were significantly higher in the heparin group compared with the thrombolytic group (22 vs. 17 mmHg, p < 0.05, and 351 vs. 171 dynes s- 1 cm- 5, p < 0.02, respectively). During exercise both parameters rose to a significantly higher level in the heparin group (from rest to exercise, PA: 22-32 mmHg, p < 0.01; PVR: 351-437 dynes s- 1 cm- 5, p < 0.01, respectively), but not in the thrombolytic group (rest to exercise, PA: 17-19 mmHg, p = NS; PVR: 171-179 dynes s- 1 cm- 5, p = NS). It is concluded that thrombolytic therapy preserves the normal hemodynamic response to exercise in the long term and may prevent recurrences of venous thromboembolism and the development of pulmonary hypertension.

Relation of the electrocardiogram to hemodynamic alterations in pulmonary embolism

Abstract In 20 consecutive cases of pulmonary embolism in a group of patients free of underlying cardiopulmonary disease the frequency of electrocardiographic changes was observed and related to hemodynamic status. A wide range of embolic obstruction (13 to 68 percent) was shown by angiography and was accompanied by hemodynamic abnormalities ranging from minimal impairment to acute cor pulmonale. Only 1 patient showed diagnostic electrocardiographic changes of right ventricular strain; in 3 the electrocardiogram was suggestive. All 4 had the hemodynamic findings of acute cor pulmonale. No. other patient did. It was clinically clear in all 4 patients that a cardiopulmonary catastrophe had occurred, and the diagnoses of acute myocardial infarction and acute massive pulmonary embolism were immediately considered. It was concluded (1) that the electrocardiogram had virtually no role in arousing the clinical suspicion of pulmonary embolism in patients free of prior cardiopulmonary disease and (2) that the only role of the electrocardiogram may be in distinguishing between the 2 most frequent cardiopulmonary catastrophes: acute myocardial infarction and acute massive pulmonary embolism.

The Ratio of Pulmonary Arterial Pressure to Pulmonary Vascular Obstruction: Index of Preembolic Cardiopulmonary Status

The magnitude of embolic obstruction by pulmonary angiographic studies has been shown to be directly related to the hemodynamic status after pulmonary embolism in patients free of prior cardiopulmonary disease; however, in patients with prior cardiopulmonary disease, the hemodynamic status after embolism may be determined either by the preembolic hemodynamic status, the magnitude of embolic obstruction, or both. No reliable index has been available to help determine the relative roles of embolism and preembolic hemodynamic disturbances in the postembolic hemodynamic status. The present study suggests that the ratio of the mean pulmonary arterial pressure to the pulmonary angiographic obstruction may effectively distinguish those patients in whom pulmonary embolism is the primary determinant of the postembolic hemodynamic abnormality from those in whom the preembolic hemodynamic abnormalities play the dominant role.

Characteristics of peak aerobic capacity in symptomatic and asymptomatic subjects with left ventricular dysfunction

Expired gas analysis was used to determine the aerobic exercise performance of subjects with depressed left ventricular (LV) systolic function and congestive heart failure (CHF). To determine whether subjects with no or minimal CHF have better aerobic exercise performance than do those with overt CHF, oxygen consumption (VO2) at anaerobic threshold (AT) and peak exercise was measured in 184 subjects with LV ejection fraction less than or equal to 0.35 who participated in the Studies of Left Ventricular Dysfunction. Subjects were divided into those with overt CHF needing treatment (treatment trial; n = 20) and those who had neither overt CHF nor treatment for CHF (prevention trial; n = 164). Treatment trial subjects had a lower LV ejection fraction (0.25 +/- 0.07) than did prevention trial ones (0.29 +/- 0.05; p = 0.001), but there were no differences in age, gender, body weight, resting heart rate and blood pressure. Treadmill exercise testing was performed after 2 to 3 weeks of placebo (no angiotensin-converting enzyme inhibitor) treatment. Treatment trial subjects exercised for a shorter time (493 +/- 160 seconds) and attained a lower peak VO2 (13 +/- 4 ml/kg/min) and VO2 at AT (11 +/- 4 ml/kg/min) than did prevention trial ones (842 +/- 277 seconds, and 20 +/- 6 and 16 +/- 5 ml/kg/min, respectively). Analysis of covariance showed that the differences in peak VO2 and VO2 at AT were statistically significant between the 2 trials after adjusting for age, gender, LV ejection fraction and New York Heart Association functional class.(ABSTRACT TRUNCATED AT 250 WORDS)