Prognostic importance of cardiac arrhythmias in systemic sclerosis.

Ambulatory electrocardiography was performed in 183 patients with systemic sclerosis recruited from five centers who were selected to reflect a balanced population with respect to disease extent and duration. Ventricular ectopy occurred in 67 percent of patients and was strongly correlated by both univariate and multivariate analyses with total mortality and with sudden death. By multivariate analysis, ventricular ectopy was strongly associated with increasing patient age and with other evidence of cardiac and pulmonary involvement but not with clinical and laboratory measures of duration and extent of systemic sclerosis. Evidence of myocardial fibrosis thought to be secondary to microvascular alteration is common in systemic sclerosis, but the clinical implications of myocardial involvement are less well appreciated. The present data suggest the need for ambulatory electrocardiography in the clinical assessment of selected patients with systemic sclerosis, especially those with cardiac or pulmonary involvement, as well as for studies of the effects of antiarrhythmic therapy.

Association between leukocyte count and the presence and extent of coronary atherosclerosis as determined by coronary arteriography.

Angiographic evidence of coronary artery disease (CAD) was correlated with leukocyte count (WBC), red cell count (RBC), cigarette smoking, age, sex, and cholesterol and triglyceride concentrations in 573 patients who underwent coronary arteriography and who did not have evidence of infection or recent myocardial infarction. Smokers had a higher WBC (7,449 +/- 1,964 leukocytes/mm3 vs 6,533 +/- 1,557, p = 0.0001) and RBC (4.921 X 10(6) +/- 0.491 X 10(6) erythrocytes/mm3 vs 4.753 X 10(6) +/- 0.480 X 10(6) p = 0.0001) than nonsmokers. Patients with CAD had a higher WBC (7,280 +/- 1,926 vs 6,664 +/- 1,700, p = 0.0005) and RBC (4.903 X 10(6) +/- 0.488 vs 4.777 X 10(6) +/- 0.485 X 10(6), p = 0.0062) than those with normal coronary arteriograms. A positive correlation between WBC and the severity of CAD (sum of arterial diameter narrowing) was noted (r = 0.16, p = 0.0001). Multiple regression showed an independent contribution of WBC in predicting severity of CAD (F = 9.26, p = 0.0025), after accounting for the effects of age, sex, serum cholesterol and triglyceride levels. When smoking was entered into the equation, the contribution of WBC in predicting the severity of angiographic CAD became weaker (F = 4.46, p = 0.035). Similar relations were seen when only smokers were analyzed and when patients with history of remote myocardial infarction were excluded. In nonsmokers these associations became either insignificant or much weaker. Thus, the relation of WBC, and RBC with CAD is mainly due to the elevation of WBC and RBC and the increase of CAD risk induced by cigarette smoking.

Current approach to treatment of primary pulmonary hypertension.

Based upon our experience with a cohort of 46 patients referred to the UCHSC from April, 1980 to April, 1987 for evaluation and treatment of PPH, we currently assess acute pulmonary vasoreactivity as defined by the patient's response to intravenous PGI2 during the initial diagnostic catheterization. A 3 to 5 day trial of high dose oral diltiazem treatment (720 mg/day maximum) is given while monitoring the patient in the clinical research center to detect significant side effects including arrhythmias, orthostatic systemic hypotension, arterial desaturation, and worsened right ventricular dysfunction. We believe it is necessary to recatheterize each patient to establish the efficacy of calcium antagonist treatment prior to discharge. Those patients who are responsive to diltiazem are discharged and followed in our pulmonary hypertension clinic. Since an occasional patient will deteriorate after several weeks of therapy, repeat right heart catheterization after 8 weeks of treatment is used to determine which patients should be continued on diltiazem for chronic therapy. Approximately 30 percent of our patients with PPH have been improved on diltiazem treatment. Most patients who have a good response to treatment after eight weeks continue to benefit from long-term treatment. It appears that the response to an acute infusion of PGI2 is useful in safely identifying those PPH patients who are likely to benefit from vasodilator therapy. Debilitated patients who are unresponsive to PGI2 and vasodilator therapy are considered potential candidates for cardiopulmonary transplantation.

Intracoronary streptokinase therapy in the coronary care unit for acute myocardial infarction.

Intracoronary streptokinase was offered and preliminary coronary angiography performed in 14 patients who were seen with the clinical diagnosis of acute myocardial infarction within 4 h of onset of symptoms. The procedure was performed in the Coronary Care Unit (CCU) of St. Peter's Medical Center with the use of a portable C-arm fluoroscope. Angiography was recorded on video tape. Service was provided by an "on-call" team consisting of two physicians, a CCU nurse, and a radiology technician, on a 24-h service basis. Adequate visualization of coronary anatomy was obtained in all patients. Patency of occluded vessels was achieved in 10 of 11 patients who received intracoronary streptokinase. The initial streptokinase bolus was administered at a mean interval of 4.1 h from onset of symptoms. It is concluded that speedy and effective coronary thrombolytic therapy can be provided in the CCU on a 24-h service basis by an on-call team. The use of CCU for this purpose will make this therapy widely available across the country, without the need for Cardiac Catheterization Laboratory.

The case for treatment of selected patients with primary pulmonary hypertension.

The treatment of primary pulmonary hypertension with pulmonary vasodilator agents is controversial. Some patients have benefited, while others have not. To shed light on the mater we reviewed published reports of 117 patients having acute vasodilator challenge and found that 53 reduced their pulmonary vascular resistance by 30% or more. Calcium antagonists (n = 46), hydralazine (n = 23), and diazoxide (n = 18) gave approximately equivalent acute reductions in resistance (30%, 35%, 32%, respectively), but captopril (n = 17) gave a poor response (-7%). The reports indicated that chronic treatment (3 months or longer) benefited only 4 of 64 patients (6%) having acute reduction in resistances of less than 30%. However, when resistance was lowered acutely by more than 30%, 33 of 53 patients (62%) improved with treatment. In 5 patients having multiple catheterization, improvement was sustained for the duration of follow-up (10 to 48 months). Except for captopril, the agents employed gave similar reductions in resistance, and perhaps the choice should be determined by avoidance of side-effects. Long-term benefit is never certain, but selecting patients with brisk acute vasodilator responses may predict the benefit from chronic vasodilator treatment.

Acute hemodynamic effects of ketanserin in pulmonary hypertension secondary to systemic sclerosis.

A selective antagonist of S2-serotonergic receptors, ketanserin, was administered intravenously during right heart catheterization to 14 patients with pulmonary hypertension complicating systemic sclerosis. A significant reduction in pulmonary vascular resistance was noted which was accompanied by an increase in cardiac output. Paradoxical increase of pulmonary artery pressure occurred in 3 patients, whereas 2 patients with mild pulmonary hypertension normalized both pulmonary pressure and vascular resistance. Our data support the hypothesis that serotonin, released during in vivo platelet activation, influences pulmonary vascular tone in systemic sclerosis.

Early partial systolic closure of the pulmonic valve relates to severity of pulmonary hypertension.

Ultrasound studies in pulmonary hypertension often show systolic partial closure of the pulmonic valve and early peaking of Doppler pulmonary flow velocity, but these findings are poorly understood. Our initial observations of earlier systolic partial closure with higher pulmonary pressures suggested that this phenomenon might relate to pressure. In 30 patients with documented pulmonary hypertension, the timing of systolic partial closure and the corresponding decrease in Doppler flow velocity related inversely to pulmonary artery pressure at catheterization. Peak flow preceded the systolic velocity decrease and also related inversely to pressure. Since changing flow velocity might reflect a changing driving force across the valve, we examined simultaneous high-fidelity catheter pressure tracings from the right ventricle and pulmonary artery from 24 patients with and without pulmonary hypertension. In 30 studies, a positive right ventricular to pulmonary artery pressure gradient was present early in systole, but the gradient decreased to a minimum value in mid-to-late systole. The timing of this minimum also related inversely to pressure. We conjectured that forces opposing ejection occur earlier in pulmonary hypertension, thereby decreasing the forward driving force and allowing earlier partial systolic closure.

Operation Everest II: cardiac filling pressures during cycle exercise at sea level.

To examine the relationship between cardiac filling pressures during exercise in man and oxygen transport, we examined sea level data from Operation Everest II. The results showed that, (1) both right atrial and wedge pressures rose with heavy exercise in normal man, (2) the magnitude of the rise in these filling pressures related both to stroke volume and maximum exercise capacity, (3) wedge pressure was tightly coupled to right atrial pressure, with each mm Hg increase in right atrial pressure resulting in a 1.4 mm Hg increase in wedge pressure, and (4) very high wedge pressures occurred (in some subjects greater than 30 mm Hg), which contributed to an elevation of pulmonary arterial pressure. Thus direct measurements indicate right heart filling pressure increases with exertion in normal man, probably providing the necessary right heart output to fill the left heart. We speculated that the high cardiac filling pressures might be needed to maintain oxygen transport during heavy exercise, and that such pressures could contribute both to elevated pulmonary arterial pressure and to increased filtration of water into the lung.