Vijay G. Kalaria

Effect of mitral regurgitation on left ventricular thrombus formation in dilated cardiomyopathy

To assess whether the presence of mitral regurgitation has a protective effect on left ventricular thrombus formation in a heterogeneous group of patients with dilated cardiomyopathy, a group of 103 patients with dilated cardiomyopathy identified by means of echocardiographic criteria was assembled over 1 year. The purpose of the study was to define a subgroup of patients with dilated cardiomyopathy from whom long-term anticoagulation might be withheld. Each echocardiogram was evaluated for the presence of left ventricular thrombus, presence and severity of mitral regurgitation, and ejection fraction. The role of clinical factors and clotting factors in left ventricular thrombus formation was assessed. Left ventricular thrombus was not present in 91 patients (group A) and was present in 12 patients (group B). Group B had larger left atrial and left ventricular systolic dimensions and decreased left ventricular systolic function. Mitral regurgitation jet area and ratio between mitral regurgitation jet area and left atrial area were lower (signifying less severe mitral regurgitation) among patients in group B. Although mitral regurgitation was equally present in group A and group B, severe mitral regurgitation was found only in group A patients ( 11 of 91 patients). Among patients with dilated cardiomyopathy, left ventricular ejection fraction is the factor most associated with left ventricular thrombus formation. The presence of severe mitral regurgitation may have a protective role in left ventricular thrombus formation.

Emergency room administration of Eptifibatide before primary angioplasty for st elevation acute myocardial infarction and its effect on baseline coronary flow and procedure outcomes

S randomized trials and a meta-analysis have shown the superiority of primary angioplasty over thrombolytic therapy for treatment of ST elevation acute myocardial infarction (AMI).1–4 Two large registries representative of practice in a community setting, however, failed to confirm a significant benefit for primary angioplasty over thrombolytic therapy.5,6 It has been postulated that a major reason for the discrepancy in the randomized trial data and so-called “real-world” primary angioplasty is an increased delay in treatment in the less controlled settings.7 Furthermore, primary angioplasty is not available to many patients due to initial presentation to a hospital without angioplasty or cardiac catheterization facilities. Recently, there has been interest in facilitated primary angioplasty, where patients are treated with fibrinolytic agents, glycoprotein (GP) IIb/IIIa inhibitors, or a combination of these agents before baseline angiography. One potential advantage of these strategies is widening of the therapeutic window for revascularization by the provision of partial reperfusion. The present study evaluates the effects of emergency room administration of the GP IIb/IIIa inhibitor, eptifibatide, before primary angioplasty on baseline coronary flow, procedure results, and in-hospital outcomes. • • • The treatment group (group 1) consisted of 30 consecutive patients who presented to our institution with AMI within 6 hours of symptom onset, were referred for primary angioplasty, and provided informed consent from December 1999 to April 2000. The controls (group 2) included 30 patients who were treated with primary angioplasty, including GP IIb/ IIIa inhibitors at the time of angioplasty, at our institution from January 1999 to November 1999. Group 2 patients were matched 1:1 with group 1 patients for age, AMI location, diabetes, gender, and time from onset of symptoms to presentation in descending order of priority. Eptifibatide was administered as a bolus of 180 mg/kg followed by a 2 mg/kg/min infusion. Patients were then referred to the cardiac catheterization laboratory and the bolus dose of eptifibatide was repeated on arrival. Baseline quantitative angiography was performed using a computer edge detection system (Artrek, Quinton Imaging, Bothell, Washington), and Thrombolysis in Myocardial Infarction (TIMI) flow grade and corrected TIMI frame counts8 were assessed by independent review of the study angiograms by 1 investigator who was blinded to the type of treatment. The primary end point was the percentage of patients with TIMI 2 or TIMI 3 coronary flow at baseline angiography. Secondary end points included percentage of patients with TIMI 3 flow, mean corrected TIMI frame count, time from baseline angiography to first balloon inflation, total procedure time, total fluoroscopy time, and total stent length per lesion. Continuous variables were compared using Student’s t test. Frequencies were compared using the chi-square test or Fisher’s exact test. Mean age was 57 years and 25% of patients were women. Comparative baseline clinical and angiographic characteristics are listed in Tables 1 and 2, respectively. Baseline TIMI 2 or TIMI 3 flow was present in 57% (95% confidence intervals 39% to 74%) of group 1 patients compared with 13% (95% confidence intervals 1% to 26%) of group 2 patients (p ,0.01) (Figure 1). The mean time from baseline angiography to initial balloon inflation and total procedure times were significantly less for group 1 patients. This difference in time to first balloon inflation was also evident for patients with persistent total occlusion of the infarctrelated artery (TIMI grade 0 flow, 11.3% vs 21.6%, p ,0.01). Other procedural outcomes are listed in Table 3 and in-hospital outcomes are shown in Table 4.5 • • • The results of this study show that for patients undergoing primary angioplasty for ST elevation AMI, a strategy of administering the GP IIb/IIIa inhibitor, eptifibatide, early after presentation and before arrival in the cardiac catheterization laboratory provides partial reperfusion and may decrease procedure complexity. Of 30 patients who received eptifibatide administered as a double bolus of 180 mg/kg with the initial bolus given 51 6 27 minutes before baseline angiography, 17 (56.7%) had TIMI 2 or 3 flow. In addition, the time from baseline angiography to first balloon inflation was significantly less for these paFrom the Department of Medicine and Cardiology Unit, University of Rochester Medical Center, Rochester, New York. This study was supported by an educational grant from COR Therapeutics, South San Francisco, California. Dr. Cutlip’s address is: Cardiology Unit, Box 679, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, New York 14642. E-mail: donald_cutlip@urmc.rochester. edu. Manuscript received October 24, 2000; revised manuscript received and accepted February 1, 2001.

Gender-related differences in thrombogenic factors predicting recurrent cardiac events in patients after acute myocardial infarction∗☆

Abstract Thrombosis contributes to recurrent coronary events in patients after acute myocardial infarction (AMI), but prognostic significance of thrombogenic factors by gender is unknown. This study aimed to determine gender-related differences in the prognostic significance of thrombogenic factors for predicting cardiac events (nonfatal reinfarction or cardiac death) in postinfarction patients. Blood levels of the following factors were measured 2 months after AMI in 791 men and 254 women: fibrinogen, von Willebrand factor, factor VII and VIIa, plasminogen activator inhibitor, D-dimer, cholesterol, apolipoprotein A-1, apolipoprotein B, lipoprotein(a), triglycerides, and high-density lipoprotein cholesterol. After adjustment for clinical covariates, levels of apolipoprotein A, high-density lipoprotein cholesterol, fibrinogen, and factor VIIa were significantly higher in postinfarction women than men. During a mean 26-month follow-up, there were 67 cardiac events (8.5%) in men and 14 (5.5%) in women (p = 0.11). In the multivariate Cox model, elevated levels of factor VIIa were a significant predictor of cardiac events in women (p = 0.022) but not in men (p = 0.80), with significant gender-related effect (hazard ratio 2.80 vs 0.92, respectively; p

Comparability of nonlinear measures of heart rate variability between long- and short-term electrocardiographic recordings.

N nonlinear measurements of heart rate variability (HRV) may reveal subtle changes in heart rate dynamics and the data support their superiority over conventional methods of HRV in predicting adverse cardiac events.1,2 Recent data on postinfarction patients with depressed left ventricular function suggest that the reduced short-term scaling exponent (a1) is a more powerful predictor of mortality than the traditional measurements of HRV.1,2 The studies evaluating the value of these methods in risk assessment have usually been done with 24-hour electrocardiographic (ECG) recordings.1,2 It would be important to know if similar information could be obtained from short-term ECG recordings. The comparability of conventional HRV measures derived from longversus short-term ECG recordings is quite good.3,4 However, the data on the comparability of the newer nonlinear measures of HRV obtained from longversus shortterm ECG recordings are very limited. The present study compares results of nonlinear HRV analysis performed in longversus short-term ECG recordings in healthy subjects and in postinfarction patients and determines which nonlinear dynamic parameters obtained from short-term recordings reliably reflect information provided by long-term recordings. • • • The study population consisted of 30 healthy subjects and 30 postinfarction patients. The healthy subjects (age 33 6 16 years [mean 6 SD], 15 men and 15 women, body mass index 24 6 3 kg/m [mean 6 SD], 9 smokers) had normal 12-lead ECG findings, did not have any evidence of disease or other health problems, did not have symptom, and were not on medication. The clinical characteristics of postinfarction patients are shown in Table 1. ECG data were recorded using the Burdick Holter recorder (Spacelab-Burdick, Milton, Wisconsin) allowing for 20 minutes of high-resolution research electrocardiography (1,000 Hz) followed by 24 hours of continuous ECG recording (200 Hz). ECG recordings were performed during the hospital stay for the postinfarction patients. However, for 24-hour and 20minute ECG recordings, the resolution of the tachogram used for HRV analysis was 5 ms. During the 20-minute recordings, the study subjects were in supine resting position. ECG data were transferred to a microcomputer for processing and HRV analysis. Premature beats and noise were excluded automatically and manually. HRV was analyzed by a software package with methods that have been previously described.5–8 Because of differences in autonomic tone under resting and ambulatory conditions, the 24-hour HRV data were compared with 2 different types of 10-minute HRV data: (1) 10-minute data obtained from the beginning of the 20-minute resting state recordings, and (2) 10-minute data obtained from the beginning of the 24-hour ambulatory data. All the time-domain and nonlinear measures of HRV were analyzed in 600-second blocks and the average values were used for comparisons. SD of all normal-to-normal RR intervals (SDNN), the square root of the mean squared differences of successive normal-to-normal RR intervals (RMSSD), and the proportion of interval differences of successive normal-to-normal RR intervals .50 ms (pNN50) were calculated as standard time-domain measures of HRV. The ratio of the low-frequency (LF, 0.04 to 0.15 Hz) component to the high-frequency (HF, 0.15 to 0.40 Hz) component of spectral power (LF/HF ratio) obtained by using the fast Fourier transformation method was determined as a frequency-domain measure of HRV. The analysis was done in 512-beat blocks. In the present study, 2 nonlinear HRV parameters From the Cardiology Unit, Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, New York; and the Division of Cardiology, Department of Medicine, University of Oulu, Oulu, Finland. This study was supported in part by grants from the Academy of Finland, the Paavo Nurmi Foundation and the Maritza and Reino Salonen Foundation, Helsinki, Finland. Dr. Perkiomaki’s address is: Cardiology Unit, Department of Medicine, University of Rochester Medical Center, 601 Elmwood Avenue, Box 653, Rochester, New York 14642. E-mail: heartjsp@heart.rochester.edu. Manuscript received September 14, 2000; revised manuscript received and accepted October 26, 2000. TABLE 1 Clinical Characteristics of the Postinfarction Patients