John C. Gurley

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

BackgroundNecropsy 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 ResultsWe 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. ConclusionsThese data establish that intravascular ultrasound is feasible and safe and yields luminal measurements that correlate generally with angiography. Differences between angiographic and ultrasonic 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.

Prognostic value of Doppler transmitral flow patterns in patients with congestive heart failure

OBJECTIVES This study was designed to determine whether Doppler echocardiographic transmitral flow patterns can predict cardiac mortality in patients with congestive heart failure. BACKGROUND Previous studies have indicated that Doppler transmitral flow patterns are related to New York Heart Association functional class and exercise capacity in patients with congestive heart failure. However, the prognostic significance of these flow patterns is not known. METHODS We analyzed the relation of transmitral flow patterns and cardiac mortality in 100 consecutive patients (76 men, 24 women; mean [+/- SD] age 60 +/- 11 years) with congestive heart failure symptoms and left ventricular ejection fraction < 40%. At the time of entry into the study, functional class and ejection fraction by radionuclide angiography were determined, and Doppler echocardiography was performed in all patients. Transmitral flow was obtained from the apical four-chamber view at the mitral annulus level. Measurements included early (E) and atrial (A) filling velocities, E/A ratio and deceleration time of the E wave. The patients were assigned to two groups according to E/A ratio or deceleration time of transmitral flow patterns, or both: a non-restrictive group (42 patients) with E/A < or = 1 or E/A = 1 to 2 and deceleration time > 140 ms, and a restrictive group (58 patients) with E/A > or = 2 or E/A = 1 to 2 and deceleration time < or = 140 ms. RESULTS Of 100 patients, 26 died during a mean follow-up period of 16 +/- 8 months. The cumulative cardiac mortality rate determined by the Kaplan-Meier method was 14% at 1 year and 35% at 2 years. Cox proportional hazards model analysis revealed that transmitral flow (restrictive vs. nonrestrictive, chi-square 6.99, p = 0.008), patient gender (female vs. male, chi-square 4.59, p = 0.03) and New York Heart Association functional class (IV vs. II, chi-square 3.95, p = 0.05) were significantly related to cardiac mortality in patients with congestive heart failure. Mortality rate in the restrictive group was markedly higher than that in the nonrestrictive group at 1 year (19% vs. 5%, respectively, p < 0.05) and at 2 years (51% vs. 5%, respectively, p < 0.01) by log-rank test. Relative risk for cardiac death was estimated as 4.1 at 1 year and 8.6 at 2 years in the restrictive group compared with the nonrestrictive group. CONCLUSIONS In patients with congestive heart failure, a restrictive transmitral flow pattern, female gender and advanced functional class are predictive of higher cardiac mortality. The restrictive transmitral flow pattern by Doppler echocardiography is the single best clinical predictor for cardiac death in patients with congestive heart failure.

Application of a new phased-array ultrasound imaging catheter in the assessment of vascular dimensions. In vivo comparison to cineangiography.

Tomographic imaging techniques such as ultrasound can provide important information in the evaluation of vascular anatomy. Recent technical advances have permitted fabrication of a small (1.83 mm), phased-array, intravascular ultrasonic imaging catheter capable of continuous real-time, cross-sectional imaging of blood vessels. We used this imaging catheter to compare intraluminal ultrasound with cineangiography in the measurement of vascular dimensions in animals and to assess the intraobserver and interobserver variability of the technique. Segmental deformation of vessel anatomy was produced by stenoses created with a tissue ligature or by balloon dilation. The mean value for measurements of vessel diameter was 5.6 mm by cineangiography and 5.7 mm by intravascular ultrasound. The correlation between cineangiography and ultrasound was close (r = 0.98). Mean cross-sectional area by angiography was 28.8 mm2 and 29.6 mm2 (r = 0.96) by ultrasound. Percent diameter reduction produced by the stenoses averaged 48.4% by cineangiography and 40.1% by ultrasound, and the two methods correlated closely (r = 0.89). Correlation between cineangiography and ultrasound for vessel diameter and area before balloon dilation was closer (r = 0.92 and 0.88) than after balloon dilation (r = 0.86 and 0.81). This difference reflected an increase in measured vessel eccentricity following balloon dilation. These data demonstrate that intravascular ultrasound is an accurate and reproducible method for measurement of vascular diameter and cross-sectional area in vivo. Intravascular ultrasound is capable of accurately identifying and quantifying segmental deformation of vascular dimensions produced by either stenoses or balloon dilation.

A Prospective, Single-Arm, Multicenter Trial of Ultrasound-Facilitated, Catheter-Directed, Low-Dose Fibrinolysis for Acute Massive and Submassive Pulmonary Embolism : The SEATTLE II Study

OBJECTIVES This study conducted a prospective, single-arm, multicenter trial to evaluate the safety and efficacy of ultrasound-facilitated, catheter-directed, low-dose fibrinolysis, using the EkoSonic Endovascular System (EKOS, Bothell, Washington). BACKGROUND Systemic fibrinolysis for acute pulmonary embolism (PE) reduces cardiovascular collapse but causes hemorrhagic stroke at a rate exceeding 2%. METHODS Eligible patients had a proximal PE and a right ventricular (RV)-to-left ventricular (LV) diameter ratio ≥0.9 on chest computed tomography (CT). We included 150 patients with acute massive (n = 31) or submassive (n = 119) PE. We used 24 mg of tissue-plasminogen activator (t-PA) administered either as 1 mg/h for 24 h with a unilateral catheter or 1 mg/h/catheter for 12 h with bilateral catheters. The primary safety outcome was major bleeding within 72 h of procedure initiation. The primary efficacy outcome was the change in the chest CT-measured RV/LV diameter ratio within 48 h of procedure initiation. RESULTS Mean RV/LV diameter ratio decreased from baseline to 48 h post-procedure (1.55 vs. 1.13; mean difference, -0.42; p < 0.0001). Mean pulmonary artery systolic pressure (51.4 mm Hg vs. 36.9 mm Hg; p < 0.0001) and modified Miller Index score (22.5 vs. 15.8; p < 0.0001) also decreased post-procedure. One GUSTO (Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries)-defined severe bleed (groin hematoma with transient hypotension) and 16 GUSTO-defined moderate bleeding events occurred in 15 patients (10%). No patient experienced intracranial hemorrhage. CONCLUSIONS Ultrasound-facilitated, catheter-directed, low-dose fibrinolysis decreased RV dilation, reduced pulmonary hypertension, decreased anatomic thrombus burden, and minimized intracranial hemorrhage in patients with acute massive and submassive PE. (A Prospective, Single-arm, Multi-center Trial of EkoSonic® Endovascular System and Activase for Treatment of Acute Pulmonary Embolism (PE) [SEATTLE II]; NCT01513759).

Increased mortality among patients taking digoxin—analysis from the AFFIRM study

AIMS Digoxin is frequently used for rate control of atrial fibrillation (AF). It has, however, been associated with increased mortality. It remains unclear whether digoxin itself is responsible for the increased mortality (toxic drug effect) or whether it is prescribed to sicker patients with inherently higher mortality due to comorbidities. The goal of our study was to determine the relationship between digoxin and mortality in patients with AF. METHODS AND RESULTS The association between digoxin and mortality was assessed in patients enrolled in the AF Follow-Up Investigation of Rhythm Management (AFFIRM) trial using multivariate Cox proportional hazards models. Analyses were conducted in all patients and in subsets according to the presence or absence of heart failure (HF), as defined by a history of HF and/or an ejection fraction <40%. Digoxin was associated with an increase in all-cause mortality [estimated hazard ratio (EHR) 1.41, 95% confidence interval (CI) 1.19-1.67, P < 0.001], cardiovascular mortality (EHR 1.35, 95% CI 1.06-1.71, P = 0.016), and arrhythmic mortality (EHR 1.61, 95% CI 1.12-2.30, P = 0.009). The all-cause mortality was increased with digoxin in patients without or with HF (EHR 1.37, 95% CI 1.05-1.79, P = 0.019 and EHR 1.41, 95% CI 1.09-1.84, P = 0.010, respectively). There was no significant digoxin-gender interaction for all-cause (P = 0.70) or cardiovascular (P = 0.95) mortality. CONCLUSION Digoxin was associated with a significant increase in all-cause mortality in patients with AF after correcting for clinical characteristics and comorbidities, regardless of gender or of the presence or absence of HF. These findings call into question the widespread use of digoxin in patients with AF.

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.

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.

Application of intravascular ultrasound for detection and quantitation of coronary atherosclerosis.

Although angiography is widely utilized to assess the extent and severity of coronary artery disease (CAD), arteriography yields only a silhouette of the vessel lumen. Coronary intravascular ultrasound supplements angiography by providing a tomographic perspective of lumen geometry and vessel wall structure. Intracoronary ultrasound can now be performedin vivo utilizing small, flexible probes capable of negotiating tortuous vessles. We have performed coronary ultrasound in more than 100 patients, including a group of normal subjects, with no serious complications. Measurements of coronary lumen dimensions by angiography and ultrasound correlated closely for normal vessels (r=0.92) and for concentrically narrowed atherosclerotic vessels (r=0.90). However, the correlation between angiography and ultrasound was only fair for eccentrically narrowed arteries (r=0.79) and was poor following angioplasty (r=0.30). Coronary artery wall motion was measured by intravascular ultrasound and demonstrated significant differences between normal arteries (18% lumen area change) and atherosclerotic vessels (11% change). Coronary ultrasound demonstrated important differences in the structure of normal and altherosclerotic vessel walls. Arteries in normal subjects exhibited a thin intimal leading-edge echo (mean 0.20 mm) and subadjacent sonolucent zone (mean 0.12 mm). Atherosclerotic vessels typically demonstrated increased thickness of both structures and often exhibited dense fibrocalcific plaques that shadowed underlying anatomy. These ultrasound abnormalities were often present at angiographically normal sites. Several limitations of coronary intravascular ultrasound were apparent, including echo ‘dropout’, distortions produced by non-coaxial imaging, and inability to image small or severely narrowed vessels. Coronary intravascular ultrasound holds great promise for the detection and quantification of CAD in the clinical setting.

A new thrombolytic regimen for acute myocardial infarction using combination half dose tissue-type plasminogen activator with full dose streptokinase: A pilot study

Because a previous study utilizing a combination of recombinant tissue-type plasminogen activator (rt-PA) and urokinase demonstrated reduced reocclusion rates compared with rates obtained with rt-PA alone, this study was conducted to determine whether the combination of rt-PA and streptokinase might achieve similar results at reduced cost. Forty patients with acute myocardial infarction were treated with a 1 h infusion of rt-PA (50 mg) and streptokinase (1.5 million U) administered within 6 h (mean 3.6 +/- 1.2) of symptom onset. Emergency coronary arteriography revealed patency of the infarct-related artery in 30 (75%) of 40 patients. With the addition of coronary angioplasty in those who had unsuccessful thrombolytic reperfusion, the early patency rate was increased to 98%. In-hospital mortality rate (2.5%) and the incidence of significant bleeding requiring transfusion (15%) were low. Angiographically documented reocclusion of the infarct vessel occurred in 3 (8%) of 37 patients by day 7. Regional wall motion of the infarct zone improved by 0.9 +/- 0.9 SD/chord (p less than 0.0005), and ejection fraction increased 3.6 +/- 8% units (p less than 0.05) between immediate and day 7 studies. In contrast to the price of full dose rt-PA (

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

2,300) or rt-PA with urokinase (