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Biomedical subjects

P C Come

Publications and source records attributed to P C Come.

At least 19 recordsLinked to original sources

An experimental model of acute and subacute viral myocarditis in the pig.

Twenty-six young pigs were infected with encephalomyocarditis virus, observed clinically, studied at intervals by noninvasive and invasive methods to assess cardiac function and eventually examined pathologically. All infected animals appeared ill, usually manifesting diminished appetite, lethargy and fever. Spontaneous mortality occurred either 1 to 4 or 20 to 21 days after infection. Electrocardiographic abnormalities, seen in the majority of animals, comprised ST-T wave changes, conduction disturbances or ventricular ectopic rhythm. The majority of animals manifested echocardiographic evidence of left ventricular dilation and decreased systolic function, which improved with time in some animals. Hemodynamic studies revealed elevation of biventricular filling pressures in 3 of 10 animals; as a group, infected animals manifested significantly elevated right ventricular filling pressures. In selected animals, the feasibility of gallium scans as well as left ventriculography and coronary angiography was demonstrated. At autopsy, heart weight/body weight ratio was significantly elevated in infected animals. The heart of all but two animals showed active myocarditis associated with fibrosis and focal calcification in the later stages. In general, the cardiovascular manifestations were parallel with those seen in acute and subacute myocarditis in humans. It is concluded that encephalomyocarditis infection in the pig is a large animal model of viral myocarditis suitable for assessing alterations in the structure and function of the cardiovascular system and the effects of interventions.

Animals

Two-dimensional and Doppler echocardiographic determinants of the natural history of mitral valve narrowing in patients with rheumatic mitral stenosis: implications for follow-up.

Fifty patients with rheumatic mitral stenosis were studied with serial two-dimensional and Doppler echocardiography to determine the natural history of changes in mitral valve area and its relation to transmitral gradients and mitral valve morphology. Over the 39-month observation period (range 7 to 74 months) the decline in valve area was 0.09 +/- 0.21 cm2/year. In addition, there were significant increases in total echocardiographic score (p = 0.0001), severity of mitral anulus calcification (p = 0.05) and severity of mitral regurgitation (p = 0.0007). Patients with an echocardiographic score greater than or equal to 8 had a more progressive course. In addition, patients with a more progressive course (decline in valve area greater than or equal to 0.1 cm2/year) had a significantly greater initial mean gradient (p = 0.01), peak gradient (p = 0.007) and total echocardiographic score (p = 0.0008). Initial valve area did not correlate with the rate of stenosis progression. Of 22 patients with an echocardiographic score less than 8 and a peak mitral gradient less than 10 mm Hg, only 1 patient (5%) had a more progressive course, compared with 80% of those with a total echocardiographic score greater than or equal to 8 and a gradient greater than or equal to 10 mm Hg. The rate of mitral valve narrowing in individual patients with rheumatic mitral stenosis is variable. Patients whose valve disease progresses rapidly are those with a greater mitral valve echocardiographic score and higher peak and mean transmitral gradients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Echocardiographic evaluation of pulmonary embolism and its response to therapeutic interventions.

Imaging and Doppler echocardiography permits assessment of right ventricular size and systolic function and of pulmonary arterial pressures, and it may facilitate detection of thromboemboli within the heart or pulmonary artery. In patients with acute pulmonary embolism of sufficient severity to appreciably increase right ventricular afterload, the right ventricle becomes dilated and hypokinetic. Tricuspid regurgitation is generally apparent, but in the absence of preexisting pulmonary arterial or left heart pathology, the regurgitant flow velocity suggests only mild to mild-moderate elevation of pulmonary arterial systolic pressure. The absence of a greater degree of pulmonary hypertension reflects the inability of the previously normal, nonhypertrophied right ventricle to generate a mean pulmonary arterial pressure in excess of about 40 mm Hg. The echocardiographic abnormalities resolve during recovery from pulmonary embolism. Currently being investigated is the question of whether right heart abnormalities resolve more rapidly with thrombolytic therapy than with heparin therapy alone.

Diagnosis, Differential

Implications of echocardiographically assisted diagnosis of pericardial tamponade in contemporary medical patients: detection before hemodynamic embarrassment.

Identification of suspected pericardial tamponade and the decision to perform invasive drainage of the pericardial space have historically been based on classic bedside findings. Two-dimensional echocardiography has improved detection of pericardial effusion, but it may be excessively sensitive in evaluation of patients for hemodynamic embarrassment. Therefore, 50 consecutive medical patients were examined who were identified by echocardiography to have probable tamponade (defined as the presence of right heart chamber collapse in the presence of a pericardial effusion) and who underwent combined right-sided cardiac catheterization and percutaneous pericardiocentesis. All patients had elevated pericardial pressure. However, many had minimal evidence of hemodynamic compromise (94% had systolic blood pressure greater than or equal to 100 mm Hg and 58% had a cardiac index greater than or equal to 2.3 liters/min per m2). Pericardiocentesis resulted in hemodynamic improvement, but frequently did not alleviate dyspnea or correct tachycardia. Patients with malignancy as the cause of tamponade had a high mortality rate (the cumulative probability of survival in such patients was only 17% at 1 year). Echocardiographically assisted diagnosis of pericardial tamponade in medical patients results in the identification of a substantial subset of patients with only subtle evidence of hemodynamic compromise. This subset of patients differs sharply from medical patients described in previous reports with classic tamponade. Although the patients can be managed by invasive catheter pericardiocentesis with few complications, the natural history and the optimal management strategy for this group are not resolved.

Cardiac Catheterization

The effect of caffeine on exercise tolerance and left ventricular function in patients with coronary artery disease.

STUDY OBJECTIVE: To determine whether acute oral caffeine ingestion by patients with coronary artery disease results in decreased treadmill exercise performance or deterioration of echocardiographic measures of systolic or diastolic left ventricular function. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Referral-based cardiovascular exercise laboratory at an urban teaching hospital. PATIENTS: Thirteen volunteers with clinically stable coronary artery disease who had exercise tests after a 2-week caffeine-free washout period. Patients continued treatment with standard antianginal medications during the study period. INTERVENTIONS: Maximal exercise treadmill testing and exercise echocardiography were done at baseline, after acute ingestion of a placebo beverage (97% caffeine-free coffee), or after drinking an identical beverage containing 250 mg of caffeine sodium benzoate. MEASUREMENTS AND MAIN RESULTS: Acute ingestion of caffeine produced a serum level of 4.50 +/- 0.16 micrograms/mL, but had no effect on resting supine heart rate, blood pressure, left ventricular fractional shortening, posterior left ventricular wall thinning or peak rates of increase in left ventricular diastolic dimension. Despite a small increase in peak systolic blood pressure during exercise (baseline, 153 +/- 8; placebo, 154 +/- 8; caffeine, 161 +/- 7 mm Hg; P less than 0.05), exercise duration, time to onset of angina, and time to 0.1 mV ST depression did not differ after ingestion of placebo or caffeine. Rate-pressure product at onset of angina and onset of 0.1 mV of ST depression were also unchanged. In response to exercise, echocardiographic measures of left ventricular systolic and diastolic function were unchanged after caffeine compared with placebo ingestion. CONCLUSIONS: These data suggest that patients with exercise-induced ischemia who are receiving appropriate antianginal therapy tolerate the caffeine-equivalent of three cups of coffee without detrimental effect on intensity of ischemia, myocardial function, or exercise duration.

Adult

Pulsed Doppler evaluation of atrial mechanical function after electrical cardioversion of atrial fibrillation.

Full recovery of atrial mechanical activity may not occur immediately after successful electrical cardioversion of atrial fibrillation to sinus rhythm. To examine the time course of recovery of left atrial mechanical function, serial two-dimensional, M-mode and transmitral pulsed Doppler echocardiographic studies were performed in 21 patients after elective direct current cardioversion of atrial fibrillation of 3 weeks' to 24 months' duration (mean 5 months). Over 3 months of follow-up, there were significant increases in both peak A wave velocity (p less than 0.005) and percent atrial contribution to total left ventricular filling (p less than 0.005). Compared with values in a normal control population, peak A wave velocity and percent atrial contribution to total left ventricular filling did not return to normal until 3 weeks after cardioversion in patients who remained in sinus rhythm. Left atrial dimension also decreased over the follow-up period (p less than 0.05) in patients with persistent sinus rhythm. These results may have important implications in guiding the appropriate duration of anticoagulant therapy after cardioversion, and in clinically assessing the hemodynamic benefit of restoring sinus rhythm in an individual patient.

Aged

Pulsed Doppler echocardiographic determination of the time course of left ventricular filling: validation with cineangiography.

Several noninvasive techniques are used to evaluate left ventricular diastolic function, but none has optimally characterized the time course of left ventricular filling. We have developed a method to characterize left ventricular filling, by integrating Doppler measurements of flow velocity across the mitral valve. The purpose of the present study was to compare this new method with contrast left ventriculographic assessment of left ventricular filling. Pulsed Doppler studies were obtained within 24 hours of left ventriculography in 15 patients: three normal subjects, seven with coronary disease, two with mitral stenosis, and three with dilated cardiomyopathy. Patients with myocardial infarction, regional wall movement abnormalities, or aortic regurgitation were excluded. Doppler-derived relative left ventricular filling was compared to filling from right anterior oblique left ventriculograms. Doppler and angiographic filling curves were qualitatively different in normal subjects and in patients with mitral stenosis and cardiomyopathy. For individual patients, however, the Doppler and angiographic filling curves were qualitatively similar, with a strong correlation between Doppler and angiographic estimates of percent filling (r = 0.95; p less than 0.001). These preliminary observations suggest that Doppler echocardiography may provide a reliable assessment of the time course of left ventricular diastolic filling. Further studies are warranted and should include more patients with diverse cardiac abnormalities.

Adult

Serial assessment of mitral regurgitation by pulsed Doppler echocardiography in patients undergoing balloon aortic valvuloplasty.

Mitral regurgitation was serially assessed by pulsed Doppler echocardiography in 144 patients undergoing balloon aortic valvuloplasty for symptomatic aortic stenosis. Regurgitant scores of 0, 1, 2 and 3 were assigned to pulsed Doppler patterns corresponding to no, mild, moderate and severe mitral regurgitation, respectively. Before balloon aortic valvuloplasty, mitral regurgitant score correlated significantly (p less than 0.005) but weakly with aortic valve area (r = -0.24), left ventricular ejection fraction (r = -0.34) and left ventricular systolic pressure (r = 0.23). There was no significant correlation between mitral regurgitation and either mean catheterization or mean Doppler aortic valve gradient. Balloon aortic valvuloplasty produced significant decreases in both catheterization and Doppler mean transvalvular aortic valve gradients (56 +/- 19 to 31 +/- 12 and 60 +/- 19 to 48 +/- 16 mm Hg, respectively; both p less than 0.0001) and a significant increase (p less than 0.0001) in aortic valve area assessed by catheterization (0.6 +/- 0.2 to 0.9 +/- 0.3 cm2). Left ventricular ejection fraction did not change, but cardiac output increased (p less than 0.001) and pulmonary capillary wedge pressure decreased (p less than 0.0001). Pulsed Doppler findings of mitral regurgitation were present in 102 of the 144 patients. Eighty-eight patients had a score compatible with mild or more severe degrees of mitral regurgitation, and 49 had a score indicative of moderate or severe valvular insufficiency. In the entire group of 144 patients, mitral regurgitant score decreased significantly from 1.1 +/- 1.0 to 1.0 +/- 1.0 (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Echocardiographic assessment of cardiac chamber size and functional performance in swine.

Ninety nonanesthetized 7- to 16-week-old pigs were studied, using 2-dimensional echocardiography that permits orientation of a targeted M-mode beam perpendicular to structures being studied and allows serial studies of the same cardiac regions. Normative data were obtained and included body weight and measurements of left atrial diameter, mitral valve excursion, aortic root diameter, left ventricular end-diastolic and end-systolic diameters, and left ventricular fractional shortening. A positive correlation was found between body weight and measurements of left atrial diameter, mitral valve excursion, aortic root diameter, left ventricular end-diastolic and end-systolic diameters, and fractional shortening. A correlation was found between body weight and age. Best-fit analysis resulted in all measurements fitting either a first- or second-degree polynomial.

Age Factors

Balloon aortic valvuloplasty in 170 consecutive patients.

Between October 1, 1985, and April 1, 1988, we performed balloon aortic valvuloplasty in 170 patients (mean age [+/- SD], 77 +/- 5 years) who had symptomatic aortic stenosis. The procedure was completed successfully in 168 patients and resulted in significant increases in the mean (+/- SD) aortic-valve area (from 0.6 +/- 0.2 to 0.9 +/- 0.3 cm2) and cardiac output (from 4.6 +/- 3.4 to 4.8 +/- 1.4 liters per minute) and decreases in the peak aortic-valve pressure gradient (from 71 +/- 20 to 36 +/- 14 mm Hg) (P less than 0.01 for all three comparisons). There were six in-hospital deaths, and five patients required early aortic-valve replacement. Follow-up data were available for all patients, for a period averaging 9.1 months. In addition to the 6 patients who died in the hospital, 25 patients died an average of 6.4 +/- 5.3 months after discharge. Symptoms recurred in 44 patients; they were managed by repeat valvuloplasty in 16 patients, by aortic-valve replacement in 17, and by medical therapy in 11. At the most recent follow-up examination, the symptoms of 103 patients had improved after valvuloplasty; this number includes 15 patients with restenosis who successfully underwent redilation. Life-table analysis indicates that the probability of survival 12 months after the procedure was 74 percent. We conclude that balloon aortic valvuloplasty is an effective palliative therapy for some elderly patients with symptomatic aortic stenosis. Symptoms improve in the majority of patients; although restenosis is common, it can be managed in some patients by repeat balloon dilation.

Adult

Usefulness of noninvasive assessment of aortic stenosis before and after percutaneous aortic valvuloplasty.

Noninvasive and catheterization studies were performed in 40 patients (mean age 76 +/- 12 years) before and after percutaneous aortic valvuloplasty. Measurements included time to 1/2 carotid upstroke, left ventricular ejection time, aortic valve excursion, mean aortic valve gradient and aortic valve area assessed using the continuity equation: aortic valve area = A X V/V1, where A = left ventricular outflow tract area, V = maximal left ventricular outflow tract velocity assessed by pulsed Doppler echocardiography and V1 = peak velocity in the aortic stenotic jet assessed using continuous-wave echocardiography. In addition, mitral regurgitation was assessed by pulsed Doppler mapping techniques. Mean aortic valve gradient, cardiac output and aortic valve area, calculated using the Gorlin formula, were determined at cardiac catheterization. There were significant correlations between Doppler and catheterization measurements of aortic valve area both before (r = 0.71, p less than 0.001) and after (r = 0.85, p less than 0.0001) valvuloplasty. The relations were demonstrated to be linear by F test and met criteria for identity. There were significant increases (all p less than 0.0005) after valvuloplasty in catheterization valve area (0.60 +/- 0.21 to 0.95 +/- 0.39 cm2), Doppler valve area (0.64 +/- 0.22 to 0.91 +/- 0.37 cm2), valve excursion (0.5 +/- 0.3 to 0.8 +/- 0.3 cm) and cardiac output (4.5 +/- 1.6 to 4.9 +/- 1.7 liter/min).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Noninvasive assessment of mitral stenosis before and after percutaneous balloon mitral valvuloplasty.

Thirty-seven patients with symptomatic mitral stenosis underwent balloon dilatation of the mitral valve. Significant increases (p less than 0.001) were noted in both catheterization- and Doppler-determined valve area (0.9 +/- 0.3 to 1.8 +/- 0.8 and 0.9 +/- 0.2 to 1.7 +/- 0.5 cm2). However, catheterization and Doppler areas before and after valvuloplasty correlated less well (r = 0.51, p less than 0.002 and r = 0.47, p less than 0.005, respectively) than the catheterization-Doppler area correlation in a previous study of 59 consecutive patients with varying degrees of mitral stenosis (r = 0.84, p less than 0.001). Mitral valve area increases were independent of valve thickness estimated using 2-dimensional echocardiography. Flail mitral leaflet movement was not observed and the degree of mitral regurgitation qualitatively assessed using pulsed Doppler mapping techniques increased by greater than 1 of 4 grades in only 1 patient. The lateral mitral valve orifice diameter increased more than the anteroposterior diameter, suggesting commissural splitting as the mechanism of successful valvuloplasty. Increases (all p less than 0.0001) were noted in mitral valve EF slope (7 +/- 5 to 18 +/- 10 mm/s), excursion (11 +/- 5 to 13 +/- 4 mm), S20S interval (0.07 +/- 0.02 to 0.08 +/- 0.02 s) and cardiac output (4.2 +/- 1.3 to 5.3 +/- 2.0 liters/min). There were significant decreases (all p less than 0.001) in left atrial diameter (5.4 +/- 1.0 to 5.1 +/- 1.0 cm), mean catheterization gradient (15 +/- 5 to 8 +/- 4 mm Hg) and mean Doppler gradient (10 +/- 4 to 6 +/- 3 mm Hg).(ABSTRACT TRUNCATED AT 250 WORDS)

Catheterization

Percutaneous balloon mitral valvuloplasty in a pregnant woman with mitral stenosis.

A 39-year-old woman with symptomatic mitral stenosis underwent percutaneous mitral valvuloplasty at the end of her first trimester of pregnancy. Balloon dilatation utilizing a double 18-20 mm balloon technique resulted in improvement in mean mitral gradient (16 to 7 mmHg) and in calculated mitral valve area (1.4 to 2.4 cm2), without significant complications and with an estimated radiation exposure to the fetus of less than 0.2 rads. The procedure resulted in disappearance of symptoms of congestive heart failure and allowed for discontinuation of diuretics. The subsequent course of gestation was uncomplicated and a normal baby boy was delivered in the 36th wk. We conclude that percutaneous mitral valvuloplasty may produce successful palliation of symptoms in patients with mitral stenosis during pregnancy.

Adult

Tissue plasminogen activator and acute pulmonary embolism.

We assessed the efficacy and safety of peripheral intravenous recombinant human tissue-type plasminogen activator (rt-PA) in 47 patients with angiographically documented pulmonary embolism (PE). We administered 50 mg/2 h and, if necessary, an additional 40 mg/4 h. By 6 hours, 94% of the patients had angiographic evidence of clot lysis that was slight in 5, moderate in 12, and marked in 27 patients. Among the 34 patients with pulmonary hypertension prior to treatment, average pulmonary artery pressure decreased from 43/17 (27) to 31/13 (19) mm Hg (P less than 0.0001). The average lung scan perfusion defect decreased from 37% before therapy to 16% (P less than 0.01) after therapy among the 19 patients who had pre- and post-treatment lung scans. Of 7 patients with pre- and post-treatment imaging and Doppler echocardiograms, hypokinetic right ventricular wall movement (mild in 1, moderate in 2, and severe in 4) normalized in 5 and improved to mild hypokinesis in 2. Right ventricular diameter decreased from 3.9 +/- 1.0 to 2.0 +/- 0.5 cm (P less than 0.005). Fibrinogen decreased 33% from baseline at 2 h and 42% from baseline at 6 h. However, patients with the greatest degree of angiographic clot lysis at 2 h had a preponderance of fibrinogenolysis over fibrinolysis, demonstrated by a lower ratio of cross-linked fibrin degradation products to fibrin(ogen) degradation products (0.14 +/- 0.09 vs. 0.54 +/- 0.82) (P less than 0.04). Among selected patients, peripheral intravenous rt-PA is associated with rapid lysis of PE, improved pulmonary perfusion, and improved right ventricular function.

Biomarkers

Doppler evidence that true left ventricular-to-aortic pressure gradients exist in hypertrophic cardiomyopathy.

The etiology of systolic left ventricular-to-aortic pressure gradients in hypertrophic cardiomyopathy is still controversial. While cavity obliteration has been proposed by some investigators as the cause for recording of a high left ventricular systolic pressure, the concept of left ventricular outflow tract obstruction has received more experimental support. To investigate further whether left ventricular pressure truly exceeds aortic pressure and implies obstruction, we studied, with imaging and Doppler echocardiographic techniques, five patients with asymmetric septal hypertrophy and systolic anterior movement of the mitral valve occasionally causing it to abut upon the septum. All had outflow tract pressure gradients (peak 85 +/- 10 mm Hg) and trace to mild mitral regurgitation. Continuous wave Doppler study recorded peak flow velocities in the outflow tract (4.6 +/- 0.3 m/sec), and mitral regurgitant (mean 6.6 +/- 0.3 m/sec) jets. Aortic systolic and diastolic blood pressures were measured by cuff sphygmomanometry, and simultaneous carotid pulse tracings were recorded. The magnitude of systolic aortic pressure was determined at the time of peak velocity in the mitral regurgitant jet. Since the peak systolic pressure gradient across the mitral valve (left ventricular minus left atrial pressure) should equal 4 times the square of the peak velocity (V) in the mitral regurgitant jet, peak left ventricular systolic pressure should equal 4 x V2 plus the height of left atrial pressure at the time of peak mitral regurgitant velocity. In each case, calculations were made assuming an upper normal left atrial pressure of 10 mm Hg.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiomyopathy, Hypertrophic