Francis J. Menapace

A comparison of management patterns after acute myocardial infarction in Canada and the United States

BACKGROUNDnThere are major differences in the organization of the health care systems in Canada and the United States. We hypothesized that these differences may be accompanied by differences in patient care.nnnMETHODSnTo test our hypothesis, we compared the treatment patterns for patients with acute myocardial infarction in 19 Canadian and 93 United States hospitals participating in the Survival and Ventricular Enlargement (SAVE) study, which tested the effectiveness of captopril in this population of patients after a myocardial infarction.nnnRESULTSnIn Canada, 51 percent of the patients admitted to a participating coronary care unit had acute myocardial infarctions, as compared with only 35 percent in the United States (P < 0.001). Despite the similar clinical characteristics of the 1573 U.S. patients and 658 Canadian patients participating in the study, coronary arteriography was more commonly performed in the United States than in Canada (in 68 percent vs. 35 percent, P < 0.001), as were revascularization procedures before randomization (31 percent vs. 12 percent, P < 0.001). During an average follow-up of 42 months, these procedures were also performed more commonly in the United States than in Canada. These differences were not associated with any apparent difference in mortality (22 percent in Canada and 23 percent in the United States) or rate of reinfarction (14 percent in Canada and 13 percent in the United States), but there was a higher incidence of activity-limiting angina in Canada than in the United States (33 percent vs. 27 percent, P < 0.007).nnnCONCLUSIONSnThe threshold for the admission of patients to a coronary care unit or for the use of invasive diagnostic and therapeutic interventions in the early and late periods after an infarction is higher in Canada than in the United States. This is not associated with any apparent difference in the rate of reinfarction or survival, but is associated with a higher frequency of activity-limiting angina.

Effects of ramipril on plasma fibrinolytic balance in patients with acute anterior myocardial infarction

BACKGROUNDnThe long-term administration of ACE inhibitors to selected patients with left ventricular dysfunction appears to reduce the incidence of recurrent myocardial infarction (MI) and unstable angina pectoris. The mechanisms responsible for the reduction in ischemic events are unknown, but likely candidates include effects on the atherosclerotic process, thrombosis, and/or vascular tone.nnnMETHODS AND RESULTSnThe effects of ACE inhibitor therapy with ramipril on plasma fibrinolytic variables were assessed in 120 subjects participating in the Healing and Early Afterload Reduction Therapy (HEART) study, a double-blind, placebo-controlled trial of acute anterior MI patients who were randomly assigned within 24 hours of the onset of symptoms to receive low-dose ramipril (0.625 mg daily), full-dose ramipril (1.25 mg titrated to 10 mg/d), or placebo for 14 days. Plasma levels of plasminogen activator inhibitor-1 (PAI-1) activity and PAI-1 antigen and tissue plasminogen activator (TPA) antigen were measured before randomization and on day 14. Clinical characteristics of the three study groups were similar, as were the prerandomization plasma levels of PAI-1 antigen, PAI-1 activity, and TPA antigen. Compared with the placebo group, PAI-1 antigen levels were 44% lower (P=.004) at day 14 in the ramipril-treated patients, and PAI-1 activity levels were 22% lower (P=.02). In contrast, plasma TPA levels were not significantly different between the placebo-treated and ramipril-treated groups.nnnCONCLUSIONSnTreatment with ramipril has a significant impact on plasma fibrinolytic variables during the recovery phase after acute MI. The renin-angiotensin system appears to play an important role in the regulation of vascular fibrinolysis, and interruption of this regulatory pathway may contribute to the clinical benefits of ACE inhibitors.

Early Versus Delayed Angiotensin-Converting Enzyme Inhibition Therapy in Acute Myocardial Infarction The Healing and Early Afterload Reducing Therapy Trial

BACKGROUNDnAlthough ACE inhibitor therapy has been shown to reduce mortality in patients with acute myocardial infarction (MI), the optimal dose and the timing of its initiation have not been determined.nnnMETHODS AND RESULTSnIn a double-blind trial of 352 patients with anterior MI, we compared the safety and effectiveness of early (day 1) versus delayed (day 14) initiation of the ACE inhibitor ramipril (10 mg) on echocardiographic measures of left ventricular (LV) area and ejection fraction (EF). An early, low-dose ramipril (0.625 mg) arm was also evaluated. Clinical events did not differ. During the first 14 days, the risk of manifesting a systolic arterial pressure of < or = 90 mm Hg was increased in both ramipril groups. LVEF increased in all groups during this period, but the early, full-dose ramipril group had the greatest improvement in EF (increase: full, 4.9 +/- 10.0; low, 3.9 +/- 8.2%; delayed, 2.4 +/- 8.8%; P for trend < .05) and was the only group that did not demonstrate a significant increase in LV diastolic area.nnnCONCLUSIONSnThe results of the present study demonstrated that in patients with anterior MI, the early use of ramipril (titrated to 10 mg) attenuated LV remodeling and was associated with a prompter recovery of LVEF. The use of low-dose regimen did not prevent hypotension and had only intermediate benefits on LV size and function. The more favorable effects on LV topography of the early use of full-dose ramipril support the results of the major clinical trials, which have demonstrated an early survival benefit of ACE inhibition.

Recovery of Ventricular Function after Myocardial Infarction in the Reperfusion Era: The Healing and Early Afterload Reducing Therapy Study

A minority of patients experience progression to clinically significant left ventricular dysfunction and enlargement after myocardial infarction (1). However, patients with worsening left ventricular function after myocardial infarction are at significantly greater risk for congestive heart failure and death (2, 3). Advances in the care of acute myocardial infarction over the past decadeparticularly the use of mechanical and pharmacologic reperfusion therapieshave reduced the risk for left ventricular dysfunction (4) and improved morbidity and mortality after myocardial infarction (5). Improvements in left ventricular function can be apparent shortly after myocardial infarction and have generally been attributed to recovery from myocardial stunning (6). However, the great heterogeneity in patients after myocardial infarction underscores the importance of identifying factors that influence the progression and regression of left ventricular dysfunction. The Healing and Early Afterload Reduction Therapy (HEART) trial (7) was a randomized, double-blind study of the hemodynamic effects of early versus delayed administration of three regimens of ramipril, an angiotensin-converting enzyme (ACE) inhibitor, after myocardial infarction. Patients were followed by performing serial echocardiography within the first 24 hours after myocardial infarction and at 14 and 90 days after myocardial infarction. Patients treated with ramipril experienced significant improvements in ejection fraction at 14 days after myocardial infarction, but all echocardiographic measures of ventricular size and function were similar in the three treatment groups by 90 days (7). The present analysis assessed clinical and echocardiographic predictors of recovery of ventricular function in the 88% of patients in HEART who underwent reperfusion therapy (65% received thrombolysis alone, 15% had percutaneous transluminal coronary angioplasty alone, and 8% had both). Methods Patients The HEART study enrolled 352 patients with acute anterior Q-wave myocardial infarction. Patients with ST-segment elevation or new Q waves in two or more contiguous leads were also eligible. Patients underwent echocardiography within 24 hours after myocardial infarction (before randomization [day 1]) and at 14 and 90 days after myocardial infarction. Patients were randomly assigned to receive one of three dosing regimens of ramipril: placebo for 14 days, followed by full-dose (10 mg) ramipril; low-dose (0.625 mg) ramipril for 90 days; or full-dose ramipril for 90 days. Thus, by day 14, all patients were treated with ACE inhibition. Inclusion and exclusion criteria and details of the titration scheme and patient characteristics are described elsewhere (7). Serial echocardiographic data from days 1, 14, and 90 were available in 249 patients. Baseline data were available for an additional 12 patients who died during follow-up. Patients with day-1 echocardiograms of insufficient quality and those who were alive at 90 days but for whom echocardiograms at this time point were not available were excluded from analysis. Of the 352 patients enrolled in the study, 48 did not have echocardiograms of sufficient quality for analysis, and 18 (including 13 who died) did not have all three echocardiograms. We also excluded 25 patients who did not receive reperfusion therapy. Echocardiographic Analysis Echocardiographic measurements were made in triplicate by using a Nova Microsonics (Mahwah, New Jersey) workstation, as described elsewhere (7). The echocardiographic reader was blinded to treatment assignment. Endocardial borders from end-diastolic and end-systolic frames were digitized manually, and left ventricular volumes were assessed by using the Simpson rule method. Infarct segment length was assessed by manually tracing the akinetic or dyskinetic segment and was expressed as a percentage of the endocardial perimeter. The reproducibility of the echocardiographic measurements is reported elsewhere (7). Statistical Analysis Patients were categorized into three groups according to degree of recovery of left ventricular function. Patients were categorized as having 1) complete recovery of function if functional abnormalities observed on day 1 improved to normal [left ventricular ejection fraction > 0.55 and absence of regional akinesis or dyskinesis], 2) partial recovery of function if ejection fraction improved and the extent of regional akinesis or dyskinesis decreased from day 1, or no 3) recovery if neither of these criteria was fulfilled or death occurred before 90 days. Left ventricular enlargement (remodeling) was defined as an increase in ventricular end-diastolic volume between day 1 and day 90 and was treated as a continuous variable. Univariate and multivariate logistic regression were used to assess relationships between day 1 values and recovery of function. Values are expressed as the mean (SD). A P value less than 0.05 was considered statistically significant. Stata statistical software (Stata Corp., College Station, Texas) was used for analyses. Results Baseline Characteristics and Left Ventricular Enlargement Clinical and echocardiographic data were obtained on day 1 before randomization (Table 1). Included and excluded patients differed significantly only with regard to age (59.4 12.3 years vs. 64.2 12.9 years; P�=�0.001). Patients with partial recovery had lower ejection fraction and larger volumes than did those with no recovery or complete recovery, and patients with full recovery had shorter infarct segments than did those with partial recovery or no recovery (Table 1). Fewer patients in the complete recovery group than in the partial or no recovery groups were diabetic, but this difference was not statistically significant. The recovery groups did not significantly differ with regard to other baseline characteristics or in the distribution of drug treatment. Table 1. Baseline Characteristics of Patients by Recovery Group Recovery of Left Ventricular Function On day 1, only 9 of 261 (3.4%) patients had normal ventricular function (ejection fraction > 0.55 and no akinesis or dyskinesis). The change in left ventricular ejection fraction varied widely and improved by day 90 in 171 of 261 (66%) patients (Figure 1). The mean change in ejection fraction during this time was 0.045 0.098. Most of this change occurred in the first 14 days (mean change in ejection fraction from day 1 to 14, 0.038 0.091); minimal additional change occurred between days 14 and 90 (Table 2). Of the 252 patients with abnormal left ventricular function on day 1 (ejection fraction < 0.55 or any akinesis or dyskinesis), 13% had complete recovery of ventricular function by day 14 and 22% of patients had complete recovery by day 90. An additional 36% of patients had partial recovery of function by day 90, defined as improvement in ejection fraction from day 1 values and shortening of the akinetic or dyskinetic segment. The remaining patients had functional deterioration (decrease in ejection fraction or increase in the length of the infarct segment from day 1; 103 patients) or died (12 patients). At 90 days, 53% (132 of 249) of patients had greater than 5% improvement in ejection fraction from baseline, but only 16% (39 of 249) had a decrease in ejection fraction greater than 5%. The length of the infarct segment decreased in the group as a whole from 27.0% 10.9% at day 1 to 19.1% 13.1% at day 14 and 16.9% 13.7% at day 90. Figure 1. Distribution of change in ejection fraction from day 1 to 90. Table 2. Echocardiographic Variables throughout the Study We previously reported a statistically significant increase in ejection fraction from day 1 to 14 in patients receiving full-dose (10 mg) ramipril (7), although ejection fraction did not differ among the groups by day 90. In the current analysis, we found no differences in the percentage of patients with full recovery of function by day 14 or day 90 according to treatment group. In addition, recovery groups did not differ in time to reperfusion (Table 1) or the proportion of patients who recovered according to type of reperfusion therapy. Predictors of Recovery of Function Baseline clinical characteristics, including age, sex, and Killip class, did not predict recovery of function. In contrast, peak creatine kinase level (which occurred a mean of 27 17 hours after onset of symptoms), a crude assessment of the extent of necrosis, and left ventricular function on day 1 (ejection fraction and extent of akinesis or dyskinesis) were significant predictors of recovery of function in univariate and multivariate analyses. The percentage of patients with complete recovery of function decreased as the creatine kinase quartile increased (P for trend < 0.001) (Figure 2). In a multiple logistic regression analysis that included peak creatine kinase level, baseline ejection fraction, infarct segment length, Killip class, age, sex, and drug therapy, peak creatine kinase level remained the strongest independent predictor of recovery. Each 100-unit increase in creatine kinase level was associated with a 4.3% decreased odds of full recovery (P�=�0.001). Figure 2. Percentage of patients with complete recovery of function by increasing quartile of peak creatine kinase level. P Left Ventricular Enlargement and Recovery of Function Overall, left ventricular enlargement (remodeling) was inversely related to improvement in ejection fraction over 90 days (r = 0.27; P�<�0.001). Nevertheless, during this time, ejection fraction improved by 4.5% 9.5% despite an increase in end-diastolic volume of 5.6 25.7 mL. The majority of this change occurred in the first 14 days after myocardial infarction. Patients who recovered function demonstrated the least enlargement. Left ventricular volume decreased by 7.6 18.4 mL from day 1 to day 90 in patients with complete recovery of function, compared with an increase of 9.4 26.3 mL in all other patients (P�<�0.001). Left ventricular e

Incidence and Natural History of Left Ventricular Thrombus Following Anterior Wall Acute Myocardial Infarction

Previous studies have reported left ventricular (LV) thrombus in 20% to 56% of patients after anterior wall acute myocardial infarction (AMI). The Healing and Early Afterload Reducing Therapy (HEART) study was a prospective study comparing effects of early (24 hours) or delayed (14 days) initiation of ramipril, an angiotensin-converting enzyme inhibitor, on LV function after anterior wall AMI. This ancillary study assessed prevalence of LV thrombus. Two-dimensional echocardiography was performed on days 1, 14, and 90 after myocardial infarction. The cohort consisted of 309 patients. Q-wave anterior wall AMI occurred in 78%; 87% received reperfusion therapy. The prevalence of LV thrombus was 2 of 309 (0.6%) at day 1, 11 of 295 (3.7%) at day 14, and 7 of 283 (2.5%) at day 90. One patient had thrombus at 2 examinations. The day 1 echocardiogram was not correlated with thrombus development. LV size increased more in patients with thrombus than in those without thrombus. Patients with thrombus had more wall motion abnormality after day 1 than patients without thrombus (p = 0.03). Thus, the current prevalence of LV thrombus in anterior wall AMI is lower than previously reported, possibly due to changes in AMI management. Preservation of LV function is likely to be an important mechanism. Most thrombi are seen by 2 weeks after AMI. Resolution documented by echocardiography is frequent.

Which Is the Graft of Choice for the Right Coronary and Posterior Descending Arteries? Comparison of the Right Internal Mammary Artery and the Right Gastroepiploic Artery

BACKGROUNDnThe graft of choice for the left anterior descending coronary artery is the left internal mammary artery because of superior long-term patency. However, controversy exists regarding the graft of choice for the right coronary artery and for the posterior descending branch.nnnMETHODS AND RESULTSnTwo types of pedicled arterial grafts were used for the right coronary and the posterior descending arteries in patients undergoing coronary bypass surgery between January 1991 and September 1994. Group A comprised 114 patients with a right internal mammary artery (RIMA) graft, and group B consisted of 127 patients with an in situ right gastroepiploic artery (R-GEA) graft. Mean age was 56.9 years in group A and 63.3 years in group B; 7.9% (9 of 114) and 33.9% (43 of 127) were diabetics in groups A and B, respectively. Overall mortality was 2.6% (3 deaths) for group A and 3.9% (5 deaths) for group B (P = NS). However, the prevalence of perioperative myocardial infarction in the right coronary artery distribution was significantly higher for group A (5.3%, or 6 of 114) than for group B (0.8%, or 1 of 127; P < .05), and the reoperation rate for graft failure (from 0 to 12 months after surgery) was significantly higher for the RIMA (4.4%, or 5 of 114) than for the R-GEA (0%; P < .05). Also, the prevalence of deep sternal wound infection in diabetics was significantly higher in group A (22.2%, or 2 of 9) than in group B (4.6%, or 2 of 43; P < .05).nnnCONCLUSIONSnOur preliminary results suggest that the failure rate of the RIMA graft is significantly higher, especially if used as a pedicled graft to the posterior descending artery. The risk of sternal wound complications is greater in diabetics if both internal mammary arteries are used for grafting. Therefore, the R-GEA graft is preferred in diabetics and whenever the posterior descending artery is the target vessel.

Left ventricular size in competitive weight lifters: an echocardiographic study

ABSTRACT MENAPACE, FRANCIS J., WILLIAM J. HAMMER, THEODORE F. RITZER, KENNETH M. KESSLER, HOWARD F. WARNER, JAMES F. SPANN, and ALFRED A. BOVE. Left ventricular size in competitive weight lifters: an echocardiographic study. Med. Sci. Sports Exercise, Vol. 14, No. 1, pp. 72–75, 1982. To determine if increased left ventricular mass is present in athletes who predominantly perform isometric exercise, this study utilized echocardiograms (echo) from 13 nationally ranked weight lifters (WL) who engaged in isometric exercise while lifting. The thickness of the ventricular septum (VS), the thickness of the posterobasal free wall (LVFW), the diameter of the left ventricular cavity at end-systole (Ds) and end-diastole (Dd) were measured in the weight lifters, all of whom were free of cardiac disease. The findings were compared with 10 normal subjects (N), as well as nine patients with idiopathic hypertrophic subaortic stenosis (IHSS) and eight patients with asymmetric septal hypertrophy (ASH). The septal thickness of the weight lifters was higher than that of the normal subjects. Weight lifters resemble ASH and IHSS patients with an increased VS and a VS/LFVW ratio greater than 1.3. Although meeting the criteria for the diagnosis of hypertrophic cardiomyopathy (HCM), it is unlikely that the weight lifters had this disorder. Two measurements provide a means to separate weight lifters from patients with HCM. Septal thickness, normalized to body surface area (mm/M2), was normal in weight lifters (N=5.81 ±0.56; WL=6.81 ± 0.29; ASH=9.37±0.44; and IHSS= 10.37 ±0.48) and mass/volume ratio VS/Dd (N=0.21 ± 0.02; WL=0.28±0.01) was different from patients with ASH (VS/Dd = 0.40±0.01) or IHSS (0.48 ±0.02). Weight lifters had larger left ventricular cavities than patients with IHSS or ASH as expressed in ratios of VS/DS and VS/Dd. These data indicate that weight lifters have normal left ventricular mass/volume ratios, in spite of an increased septal/free wall ratio.

Incidence of intracranial hemorrhage complicating treatment with glycoprotein IIb/IIIa receptor inhibitors: a pooled analysis of major clinical trials

PURPOSEnThe major risk of therapy with platelet glycoprotein IIb/IIIa receptor inhibitors is bleeding. We reviewed trials using these agents to determine if bleeding risks include an increased incidence of intracranial hemorrhage.nnnMETHODSnA Medline search identified 14 randomized trials of intravenous platelet glycoprotein IIb/IIIa receptor inhibitors for patients undergoing percutaneous coronary intervention or who had an acute coronary syndrome. We compared the incidence of intracranial hemorrhage among 15,850 patients treated with glycoprotein IIb/IIIa inhibitors with that among 12,039 patients treated with placebo.nnnRESULTSnThe incidence of intracranial hemorrhage with heparin plus any IIb/IIIa inhibitor was similar to placebo with heparin (0.12% vs 0.09%, odds ratio = 1.3, 95% confidence interval: 0.6 to 3.1, P = 0.59). The incidence of intracranial hemorrhage with glycoprotein IIb/IIIa drugs alone was similar to that with heparin alone (0.07% vs 0.06%), albeit with a wide confidence interval (odds ratio = 1.2, 95% confidence interval: 0.1 to 16, P = 1.0).nnnCONCLUSIONSnIntravenous glycoprotein IIb/IIIa receptor inhibitors alone or in combination with heparin do not cause a statistically significant excess of intracranial hemorrhage as compared with heparin alone. Because of small numbers, the data do not exclude the possibility of an excess of intracranial hemorrhage in some groups of patients treated with glycoprotein IIb/IIIa receptor inhibitors.

Guidelines for cardiac sonographer education: report of the American Society of Echocardiography Sonographer Education and Training Committee.

Carolyn Janko Gardner, RDCS; Susan Brown, BS, RDMS; Sandra Hagen-Ansert, BA, RDMS, Pamela Hartigan, RDMS, Joseph Kisslo, MD, Kitty Kisslo, BS, RDMS, Oi Ling Kwan, BS, RDMS, Francis Menapace, MD, Catherine Otto, MD, Natesa Pandian, MD, Alan J. Pearlman, MD, Andrea Skelly, BS, RDCS, and Geoffrey Stevenson, MD, Seattle, Washington, . Santa Ana and San Diego, California, Durham, North Carolina, Danville, Pennsylvania, Lexington, Kentucky, Boston, Massachusetts, and Providence, Rhode Island

Accuracy of Blood Pressure Measurements Transmitted Through a Telemedicine System in Underserved Populations

In underserved populations, inadequate surveillance and treatment allows hypertension to persist until actual cardiovascular events occur. Thus, we developed an Internet-based telemedicine system to address the suboptimal control of hypertension and other modifiable risk factors. To minimize cost, the subjects used home monitors for blood pressure (BP) measurements and entered these values into the telemedicine system. We hypothesized that patients could accurately measure their BP and transmit these values via a telemedicine system. Inner city and rural subjects (N = 464; 42% African-American or Hispanic) with 10% or greater 10-year risk of cardiovascular disease and with treatable risk factors were randomized into two groups, control group (CG) and telemedicine group (TG). Each subject received a home sphygmomanometer with memory. The TG recorded and entered BP at least weekly. During office visits, the BP meters were downloaded and recorded BP compared to BP values transmitted via telemedicine. The telemedicine (T) BP values were similar to the meter recorded (R) values (T: systolic/diastolic BP 133.4 +/- 11.1/77.5 +/- 6.8 mm Hg, and R: systolic/diastolic BP 136.4 +/- 11.9.4/79.7 +/- 7.5 mm Hg). The percent error was <1% for both systolic (-0.02 +/- 0.04%) and diastolic (-0.03 +/- 0.04%) BP. Lastly, the telemedicine BP values were similar to the office (O) BP values for systolic and diastolic BP (T: systolic/diastolic BP 133.4 +/- 11.1/77.5 +/- 6.8 mm Hg, and O: systolic/diastolic BP 136.3 +/- 20.5/78.1 +/- 10.5 mm Hg). In underserved populations, this inexpensive approach of patients using a home monitor and entering these values into a telemedicine system provided accurate BP data.