Epoprostenol treatment for idiopathic pulmonary arterial hypertension in pregnancy.

Idiopathic pulmonary arterial hypertension is a rare condition associated with significant maternal mortality. We report the management of a 37-year-old multigravida with severe disease using epoprostenol, a multidisciplinary approach, and a planned delivery. Although the patient survived the pregnancy, her pulmonary function significantly worsened. Epoprostenol, a pulmonary vasodilator, should be considered when indicated during pregnancy. Neither fetal nor neonatal harm was identified.

Ambrosia beetle (Coleoptera: Scolytidae) species, flight, and attack on living eastern cottonwood trees.

In spring 2002, ambrosia beetles (Coleoptera: Scolytidae) infested an intensively managed 22-ha tree plantation on the upper coastal plain of South Carolina. Nearly 3,500 scolytids representing 28 species were captured in ethanol-baited traps from 18 June 2002 to 18 April 2004. More than 88% of total captures were exotic species. Five species [Dryoxylon onoharaensum (Murayama), Euwallacea validus (Eichhoff), Pseudopityophthorus minutissimus (Zimmermann), Xyleborus atratus Eichhoff, and Xyleborus impressus Eichhoff]) were collected in South Carolina for the first time. Of four tree species in the plantation, eastern cottonwood, Populus deltoides Bartram, was the only one attacked, with nearly 40% of the trees sustaining ambrosia beetle damage. Clone ST66 sustained more damage than clone S7C15. ST66 trees receiving fertilization were attacked more frequently than trees receiving irrigation, irrigation + fertilization, or controls, although the number of S7C15 trees attacked did not differ among treatments. The study location is near major shipping ports; our results demonstrate the necessity for intensive monitoring programs to determine the arrival, spread, ecology, and impact of exotic scolytids.

T lymphocyte beta 2-adrenergic receptor function and density after acute myocardial infarction.

The T lymphocyte beta 2-adrenergic receptor (beta 2AR) density and function were compared in 15 patients suffering acute myocardial infarction and 10 patients with stable coronary artery disease (CAD). Density was determined using radioligand binding with 125IPIN, and function by in vitro cyclic adenosine 3',5'-monophosphate (cAMP) production. In patients suffering acute myocardial infarction, T lymphocyte beta 2AR density (823.8 +/- 480 sites/cell) was slightly but not significantly different from that in patients with stable CAD (629 +/- 301 sites/cell). There was no difference in T lymphocyte cAMP production at baseline (1.11 +/- 0.70 vs 1.04 +/- 0.49 pM/10(6) cells) or after isoproterenol stimulation (2.53 +/- 1.63 vs 2.62 +/- 2.05 pM/10(6) cells), respectively. Further study is necessary to determine if beta 2AR numbers on T lymphocytes are significantly increased after acute myocardial infarction.

Echo Doppler evaluation of patients with acute mitral regurgitation: superiority of transesophageal echocardiography with color flow imaging.

Acute mitral regurgitation is a medical emergency that requires prompt, accurate diagnosis and urgent therapy. Although the use of echo Doppler imaging has been described in these patients, preliminary observations have suggested that color flow Doppler performed from the standard transthoracic windows may underestimate the severity of mitral insufficiency in this setting. The aim of this study was to compare transesophageal color Doppler quantitation of regurgitation with results obtained from standard transthoracic windows in patients with acute, severe mitral regurgitation. Two-dimensional echocardiography with pulsed, continuous, and color flow Doppler was performed by both transthoracic and transesophageal methods in 16 consecutive patients who were documented to have acute severe mitral insufficiency by catheterization. Transthoracic and transesophageal scans were reviewed by two blinded observers and assessed for the detection of mitral regurgitation by transthoracic pulsed wave (81%), continuous wave (100%), and color flow Doppler (81%) compared with transesophageal color flow imaging (100%; p = NS). Severity of mitral regurgitation was graded as none, mild, moderate, or severe on the basis of existing transthoracic pulsed wave and color flow criteria and compared with transesophageal color flow grading. At first examination patients were critically ill, with elevated pulmonary wedge pressures (mean 27 +/- 7 mm Hg) and V waves (mean 45 +/- 10 mm Hg). Fifteen of the patients underwent emergency surgery, and the overall hospital mortality rate was 12%. Maximal color flow jet areas were significantly greater on transesophageal scanning (mean 10.5 cm2) compared with transthoracic color jets (mean 2.3 cm2).(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary reactivity to nitroglycerin: intravascular ultrasound evidence for the importance of plaque distribution.

OBJECTIVES: This study was designed to assess the extent and timing of vasodilation after intracoronary administration of nitroglycerin using intravascular ultrasound. We also sought to relate the magnitude of nitroglycerin-induced dilation to the distribution of atherosclerotic plaque. BACKGROUND: Although previous angiographic studies have shown that nitroglycerin can dilate both normal and stenotic coronary arteries, it remains uncertain whether atherosclerotic vessels can respond to nitroglycerin to the same extent as normal arteries in the clinical setting. METHODS: We analyzed a total of 48 segments from 48 patients by means of a multielement 3.5F to 5.5F 20-MHz intravascular ultrasound system before and after intracoronary administration of nitroglycerin (250 micrograms). Videotaped images were digitized, and the lumen cross-sectional area was measured with an electronic cursor. In noncircumferential lesions, the perimeters of the normal and diseased portions were measured separately to compare the reactivity to nitroglycerin in each portion. RESULTS: Of 48 sites examined 14 were normal by ultrasound, and 34 revealed atherosclerotic lesions. In the 14 normal segments nitroglycerin produced a large increase in cross-sectional area (31 +/- 16% [mean +/- SD]) within 60 s after injection. In the 34 atherosclerotic segments, nitroglycerin-induced dilation was impaired, and the cross-sectional area increased only 12 +/- 8% (p < 0.01). In 15 of 34 atherosclerotic segments, a noncircumferential lesion was identified, and the cross-sectional area after nitroglycerin increased an average of 17 +/- 6%. In the remaining 19 sites, circumferential disease was present, and the cross-sectional area increased by only 8 +/- 7% (p < 0.05 vs. normal or noncircumferential atherosclerotic segments). In noncircumferential lesions, the increase in the perimeter of the normal portion of the wall was significantly greater (14 +/- 6%) than the increase in the diseased portion (5 +/- 3%, p < 0.05). CONCLUSIONS: These data indicate that vasoreactivity after nitroglycerin administration is reduced in segments with atherosclerosis by ultrasound. We suggest that nitroglycerin-induced vasodilation at the stenotic segments can be produced primarily by expansion of the nondiseased portion of the vessel wall.

Intravascular ultrasound of the coronary arteries: current applications and future directions.

Although angiography is widely applied in the diagnosis of the coronary artery disease (CAD), studies have questioned the accuracy of radiographic methods. Miniaturized intravascular ultrasound devices offer several potential advantages, including a tomographic orientation and the ability to characterize atherosclerotic plaques. Two dissimilar technical approaches to transducer design have emerged: mechanically rotated devices and multi-element arrays, each yielding small coronary catheters (1.1-1.8 mm in diameter). Initial studies of coronary ultrasound have demonstrated few serious untoward effects. In most normal subjects, the vessel wall is laminar in appearance with an intimal leading edge and subintimal sonolucent layer averaging less than or equal to 0.20 mm in thickness. In most CAD patients, the thickness of the leading-edge or sonolucent zone is abnormally increased. Atherosclerotic abnormalities are frequently evident in segments with no angiographic lesion. At sites with a circular lumen shape, minimum diameter by ultrasound and angiography correlate closely, r = 0.93. At sites with an eccentric lumen, significant disagreement between angiography and ultrasound diameter is evident, r = 0.78. Correlation between angiography and ultrasound from percent stenosis is moderate, r = 0.63. Following balloon angioplasty percutaneous transluminal coronary angioplasty (PTCA), morphologic findings include complex cracks, splits, and dissections, and minimum lumen diameter by angiography and intravascular ultrasound correlate poorly. Recent advances have improved the utility of coronary ultrasound, including smaller catheters and a device combining a miniature imaging transducer (1.16 mm) with a low profile balloon (0.028-0.033 inch). Important current limitations include inability to visualize the smallest coronaries and tight stensoses. The future of coronary ultrasound is promising, propelled by the unique capability of this modality to image atherosclerotic plaques directly.

Influence of operator- and patient-dependent variables on the suitability of automated quantitative coronary arteriography for routine clinical use.

This study was designed to elucidate the operator- and patient-dependent variables inherent in clinical application of quantitative coronary arteriography. Digital arteriograms from 25 consecutive patients undergoing diagnostic catheterization were analyzed by four experienced angiographers utilizing an automated coronary edge detection system to measure percent area stenosis. The identification of potentially significant lesions for quantitation constituted a major source of variability, with unanimous agreement on the presence of a greater than or equal to 50% stenosis occurring at 38 (29%) of the 130 reported sites. Selection of an optimal frame for quantitative analysis resulted in disagreement for every lesion reported. Frame selection by the operator, as opposed to measurement of preselected frames, increased the interobserver variability from 5% to 7% for automated geometric analysis (p less than 0.01), and from 8% to 10.5% for automated densitometric analysis (p less than 0.01). Fully automatic arterial border detection was possible for only 20 (52.5%) of the 38 unanimously identified stenoses. The 18 failures involved one or more of the following factors: 1) stenosis at a bifurcation (13 [72%]); 2) diffuse, severe disease (8 [44%]); 3) excessive vessel tortuosity or overlap or both (4 [22%]); and 4) poor image quality (5 [28%]). In contrast, the same automated border detection algorithm successfully traced all 15 preselected frames of discrete stenoses referred for coronary angioplasty. Automated quantitative coronary arteriography performs well when carefully selected, discrete stenoses are presented to the computer for analysis. However, quantitative analysis of routine clinical coronary arteriograms is limited by operator-dependent variability in stenosis identification and frame selection, as well as by complex coronary anatomy and suboptimal image quality. These limitations make automated quantitative coronary arteriography impractical for routine clinical use.

Intravascular ultrasound assessment of lumen size and wall morphology in normal subjects and patients with coronary artery disease.

BACKGROUND: Necropsy studies demonstrate that coronary artery disease (CAD) is frequently complex and eccentric. However, angiography provides only a silhouette of the vessel lumen. Intravascular ultrasound is a new tomographic imaging method for evaluation of coronary dimensions and wall morphology. Few data exist regarding intravascular ultrasound in patients with CAD, and no data exist for subjects with normal coronaries. METHODS AND RESULTS: We used a multielement 5.5F, 20-MHz ultrasound catheter to examine eight normal subjects and 43 patients with CAD. We assessed the safety of coronary ultrasound and the effect of vessel eccentricity on comparison of minimum luminal diameter by angiography and ultrasound. Normal and atherosclerotic wall morphology and stenosis severity were also evaluated by intravascular ultrasound. The only untoward effect was transient coronary spasm in five patients. At 33 sites in normal subjects, the lumen was nearly circular, yielding a close correlation between angiographic and ultrasonic minimum diameter (r = 0.92). At 90 sites in patients with CAD, ultrasound demonstrated a concentric cross section; correlation was also close (r = 0.93). However, at 72 eccentric sites, correlation was not as close (r = 0.77). For 41 stenoses, correlation between angiography and ultrasound for area reduction was moderate (r = 0.63). In normal subjects, wall morphology revealed a thin (0.30 mm or less) intimal leading edge and subadjacent sonolucent zone (0.20 mm or less). Patients with CAD exhibited increased thickness and echogenicity of the leading edge, thickened sonolucent zones, and/or attenuation of ultrasound transmission. CONCLUSIONS: These data establish that intravascular ultrasound is feasible and safe and yields luminal measurements that correlate generally with angiography. Differences between angiographic and ultrasound measures of lumen size in eccentric vessels probably reflect the dissimilar perspectives of tomographic and silhouette imaging techniques. Intravascular ultrasound provides detailed images of normal and abnormal wall morphology not previously possible in vivo.

A prospective, randomized trial comparing combination half-dose tissue-type plasminogen activator and streptokinase with full-dose tissue-type plasminogen activator. Kentucky Acute Myocardial Infarction Trial (KAMIT) Group.

BACKGROUND: The potential benefits of combination thrombolytic agents in the treatment of myocardial infarction remain uncertain. In a small pilot study, we demonstrated that combining half-dose tissue-type plasminogen activator (t-PA) with streptokinase (SK) achieved a high rate of infarct vessel patency and a low rate of reocclusion at half the cost of full-dose t-PA. METHODS AND RESULTS: We designed a prospective trial in which 216 patients were randomized within 6 hours of myocardial infarction to receive either the combination of half-dose (50 mg) t-PA with streptokinase (1.5 MU) during 1 hour or to the conventional dose of t-PA (100 mg) during 3 hours. Acute patency was determined by angiography at 90 minutes, and angioplasty was reserved for failed thrombolysis. Heparin and aspirin regimens were maintained until follow-up catheterization at day 7. Acute patency was significantly greater after t-PA/SK (79%) than with t-PA alone (64%, p less than 0.05). After angioplasty for failed thrombolysis, acute patency increased to 96% in both groups. Marked depletion of serum fibrinogen levels occurred after t-PA/SK compared with t-PA alone at 4 hours (37 +/- 36 versus 199 +/- 66 mg/dl, p less than 0.0001) and persisted 24 hours after therapy (153 +/- 66 versus 252 +/- 75 mg/dl, p less than 0.0001). Reocclusion (3% versus 10%, p = 0.06), reinfarction (0% versus 4%, p less than 0.05), and need for emergency bypass surgery (1% versus 6%, p = 0.05) tended to be less in the t-PA/SK group. Greater myocardial salvage was apparent in the t-PA/SK group as assessed by infarct zone function at day 7 (-1.9 SD/chord versus -2.3 SD/chord after t-PA alone, p less than 0.05). In-hospital mortality (6% versus 4%) and serious bleeding (12% versus 11%) were similar between the two groups. CONCLUSIONS: These results suggest that a less expensive regimen of half-dose t-PA with SK yields superior 90-minute patency and left ventricular function and a trend toward reduced reocclusion compared with the conventional dose of t-PA.

Acute effects of parenteral beta-blockade on regional ventricular function of infarct and noninfarct zones after reperfusion therapy in humans.

Although the mechanism is unknown, clinical trials have suggested that intravenous beta-adrenergic blockade may prevent early cardiac rupture after myocardial infarction. Previous studies have examined effects of beta-blockers on global left ventricular function after myocardial infarction; however, few data exist regarding their immediate effects on regional function or in patients after successful reperfusion. Therefore, 65 patients in whom thrombolysis with or without coronary angioplasty achieved reperfusion at 4.6 +/- 1.7 h from symptom onset were studied. Low osmolarity contrast ventriculograms were obtained immediately before and after administration of 15 mg of intravenous metoprolol (n = 54) or placebo (n = 11). Intravenous metoprolol immediately decreased heart rate (from 92 to 76 beats/min, p less than 0.0001), increased left ventricular diastolic volume (from 150 to 163 ml, p less than 0.001) and systolic volume (from 72 to 77 ml, p less than 0.0005) but did not change systolic and diastolic pressures. Although there was no difference in ejection fraction after metoprolol, centerline chord analysis revealed reduced noninfarct zone motion (from 0.41 to 0.12 SD/chord, p less than 0.05), improved infarct zone motion (from -3.1 to -2.9 SD/chord, p less than 0.01) and smaller circumferential extent of hypokinesia (from 30 to 27 chords, p less than 0.05). Patients with dyskinesia of the infarct zone had the most striking improvement in infarct zone wall motion. Because these changes occurred immediately after beta-blockade, they could not be attributed to myocardial salvage. No significant changes in heart rate, left ventricular volumes or regional wall motion were apparent in the control group.(ABSTRACT TRUNCATED AT 250 WORDS)

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)

Assessment of abnormal systolic intraventricular flow patterns by Doppler imaging in patients with left ventricular dyssynergy.

Few data exist regarding the consequences of abnormalities of segmental contraction on intraventricular flow patterns. The development of color Doppler flow imaging has now permitted the visualization of intraventricular blood flow patterns. Therefore, we performed Doppler flow mapping in 41 patients (12 with normal left ventricular contraction, eight with hypokinesis or akinesis, and 21 with dyskinesis) and compared these findings with left ventriculography. Systolic blood flow by Doppler mapping in subjects with normal ventricular contraction was characterized primarily by flow through the left ventricular outflow tract and into the aorta. In patients with dyskinesis, paradoxical systolic flow toward the abnormal segment was present, and persisted for at least 50% of systole in 18 of 21 patients. Mean duration of paradoxical flow in dyskinetic patients was 77% of systole. Paradoxical flow was also observed in two of five patients with akinesis but in no patients with hypokinesis. A good correlation was observed between the duration of paradoxical systolic flow and indexes of regional wall motion (radian shortening of the involved myocardium) (r = 0.77) and global ejection fraction derived from cineangiography (r = 0.79). Correlations between the area of the paradoxical systolic flow stream in midsystole and indexes of left ventricular function were less close, with r equaling 0.57 for both regional wall motion and ejection fraction. Thus, paradoxical systolic flow can be detected in most patients with left ventricular dyskinesis, and correlates with the magnitude of regional and global left ventricular dysfunction by cineangiography.

Determination of coronary flow reserve by digital angiography: validation of a practical method not requiring power injection or electrocardiographic gating.

Although coronary flow reserve is a well established measure of the physiologic significance of atherosclerotic stenosis, cumbersome methodology has prevented its widespread clinical application. This study evaluated a new simplified method of measuring coronary flow reserve based on indicator-dilution analysis of hand-injected digital coronary arteriograms. In five dogs, the circumflex artery was instrumented with an angiographic catheter, an electromagnetic flow probe and a pneumatic occluder. For each of 18 stenoses of varying severity, arteriograms were obtained under basal conditions and during papaverine-induced hyperemia. A pair of background-corrected arterial time-density curves was generated for each stenosis by off-line computer analysis of the circumflex artery arteriograms. Coronary flow reserve was calculated from the measured areas of the time-density curves and the known volume of contrast medium used to produce each curve. Angiographic flow reserve ranged from 0.9 to 6.1 (mean 2.99), whereas electromagnetic flow reserve ranged from 0.7 to 6.9 (mean 3.02). Angiographic and electromagnetic measurements of coronary flow reserve correlated well (r = 0.86). This study establishes that indicator-dilution analysis of 30 frames/s digital coronary arteriography permits the accurate determination of coronary flow reserve. The technique described employs hand injection of small doses of radiographic contrast medium using conventional catheters, and should be readily applicable to the study of human coronary artery disease.

Mechanism of acute myocardial infarction in patients with prior coronary artery bypass grafting and therapeutic implications.

Although acute myocardial infarction (AMI) is usually due to thrombotic occlusion when involving a native coronary artery, the mechanism responsible for AMI in patients with previous coronary artery bypass grafting (CABG) is not well understood. Since knowledge of pathophysiology of AMI may alter subsequent management, angiograms obtained between 1 hour and 7 days of AMI (median 1 day) were reviewed in 50 patients greater than 1 year after CABG. The culprit vessel was identified by the presence of residual stenosis and/or thrombus in the vessel supplying the infarct zone or by reviewing previous angiograms. The infarct vessel was identified as a vein graft in 38 (76%) patients, the native vessel in 8 patients (16%) and could not be accurately determined in 4 patients (8%). Among the 38 vein grafts suspected as the infarct vessel, unequivocal angiographic evidence of residual thrombus (filling defect/persistent staining) was present in 31 (82%) and was greater than 2 cm in length in 15 patients. Successful reperfusion occurred in only 2 of 8 (25%) grafts after intravenous thrombolytic therapy. Intragraft thrombolysis with or without additional angioplasty was successful at restoring flow in 8 of 10 (80%) grafts. Data indicate that in patients who have undergone previous CABG, AMI is usually caused by thrombotic occlusion of a saphenous vein graft and that conventional intravenous thrombolytic therapy may be inadequate to restore flow. The large mass of thrombus and absent flow in the graft may require subselective drug infusion, a higher thrombolytic dose or a mechanical means of recanalization.

Removal of retained intracoronary percutaneous transluminal coronary angioplasty equipment by a percutaneous twin guidewire method.

Balloon rupture during percutaneous transluminal coronary angioplasty (PTCA) resulted in embolization of a guidewire-balloon fragment into the distal circumflex artery. Access to the circumflex was technically difficult because of aortic root dilation. The fragment was removed by inserting two PTCA guidewires into the artery and twisting them together to produce a helix. The helix propagated distally, entrapping the embolized fragment for removal. This report describes an unusual mode of failure for a balloon-on-a-wire dilating catheter and a new percutaneous removal technique that may be applied to retained catheter debris in small, inaccessible vessels.

Negative inotropic effect of intravenous nifedipine in coronary artery disease: relation to plasma levels.

The relative extent of the vasodilator versus direct negative inotropic effects of nifedipine was studied in 15 male patients with documented coronary artery disease and normal left ventricular function. At the time of diagnostic cardiac catheterization, three groups of five patients received dose of 1, 2, and 3 mg intravenous nifedipine at a rate of 0.33 mg/min. Hemodynamic measurements and blood collections were made before, during, and every 5 minutes for 30 minutes after infusion of nifedipine. Heart rate increased and mean arterial pressure decreased significantly after the 2 and 3 mg doses of nifedipine. Systemic vascular resistance was significantly decreased and cardiac index increased after all doses of nifedipine. Maximal left ventricular dp/dt (dp/dtmax) was significantly decreased after the 3 mg infusion. The reduction in dp/dtmax was most consistent with a reduction in left ventricular contractility as opposed to changes in loading conditions. Plasma concentrations of nifedipine were significantly correlated with bidirectional changes in dp/dtmax (r = 0.86). Nifedipine concentrations below 28.2 ng/ml were associated with a rise in dp/dtmax, whereas concentrations above that level were associated with a reduction in dp/dtmax. These data indicate that intravenous nifedipine produces dose- and concentration-dependent depression of myocardial contractility in patients with coronary artery disease. Nifedipine concentrations associated with negative inotropic effects are readily achievable with common oral and sublingual doses.