Edward M. Dwyer

Thrombogenic Factors and Recurrent Coronary Events

BACKGROUND Thrombosis is a pivotal event in the pathogenesis of coronary disease. We hypothesized that the presence of blood factors that reflect enhanced thrombogenic activity would be associated with an increased risk of recurrent coronary events during long-term follow-up of patients who have recovered from myocardial infarction. METHODS AND RESULTS We prospectively enrolled 1045 patients 2 months after an index myocardial infarction. Baseline thrombogenic blood tests included 6 hemostatic variables (D-dimer, fibrinogen, factor VII, factor VIIa, von Willebrand factor, and plasminogen activator inhibitor-1), 7 lipid factors [cholesterol, triglycerides, HDL cholesterol, LDL cholesterol, lipoprotein(a), apolipoprotein (apo)A-I, and apoB], and insulin. Patients were followed up for an average of 26 months, with the primary end point being coronary death or nonfatal myocardial infarction, whichever occurred first. The hemostatic, lipid, and insulin parameters were dichotomized into their top and the lower 3 risk quartiles and evaluated for entry into a Cox survivorship model. High levels of D-dimer (hazard ratio, 2.43; 95% CI, 1.49, 3.97) and apoB (hazard ratio, 1.82; 95% CI, 1.10, 3.00) and low levels of apoA-I (hazard ratio, 1.84; 95% CI, 1.10, 3.08) were independently associated with recurrent coronary events in the Cox model after adjustment for 6 relevant clinical covariates. CONCLUSIONS Our findings indicate that a procoagulant state, as reflected in elevated levels of D-dimer, and disordered lipid transport, as indicated by low apoA-1 and high apoB levels, contribute independently to recurrent coronary events in postinfarction patients.

Left ventricular dysfunction after acute myocardial infarction: Results of a prospective multicenter study

In a multicenter prospective study of 866 patients who survived the coronary care unit phase of an acute myocardial infarction, variables reflecting left ventricular function were examined to assess their impact on 2 year survival. Single variables that reflected left ventricular dysfunction before infarction and in the acute and recovery phases were, respectively, history of prior myocardial infarction, rales in the coronary care unit dichotomized at greater than bibasilar and predischarge radionuclide ejection fraction dichotomized at less than 0.40. When combined in a stepwise fashion, patients lacking these three risk characteristics had a 2 year 4.2% mortality rate, whereas patients possessing all three characteristics had a 45% mortality rate. Rales in the coronary care unit and predischarge ejection fraction act independently, and each contributes to mortality. Fifty-two patients with advanced rales but an ejection fraction of 0.40 or greater had a 21% mortality rate. Similarly, 208 patients with few rales but an ejection fraction of less than 0.40 had a 15% mortality rate. These data suggest that the mortality risk imposed by those factors that assess permanent left ventricular damage is independent of and additive to the mortality risk contributed by dynamic, acute phase dysfunction. These data fit the hypothesis that acute phase dysfunction is, in part, due to transient ischemia that, on reversal, can restore function toward normal. The results suggest 1) that assessment of left ventricular function during the acute and recovery phases of myocardial infarction is necessary to define prognostic characteristics of an individual patient, and 2) that of particular importance is the identification of patients whose postinfarction course is consistent with reversible ischemia.

Nonfatal cardiac events and recurrent infarction in the year after acute myocardial infarction

The occurrence and importance of nonfatal cardiac events in the year after an acute myocardial infarction were studied in 866 patients who were enrolled by nine hospitals with a broad geographic distribution. The extensive clinical data acquired on each patient included special tests, such as radionuclide-determined ejection fraction, 24 hour ambulatory electrocardiogram and a low level exercise tolerance test. Recurrent events were frequent in the first 5 months, and certain events were significant indicators of a poor prognosis. An ejection fraction less than 40% and angina after discharge from the coronary care unit predicted patients at high risk of rehospitalization. Recurrent infarction was similarly predicted by angina, but not by any features of an exercise test. This study demonstrates the considerable morbidity that occurs after an acute myocardial infarction and its relation to and role in subsequent mortality.

Angina pectoris in patients with normal and abnormal coronary arteriograms

Abstract Ten patients with typical angina pectoris and normal coronary arteriograms were evaluated. Hemodynamic measurements and clinical features were analyzed and compared to those in a similar group of patients with angina secondary to demonstrable coronary artery disease. Both hemodynamic and clinical abnormalities were observed in those patients with angina and normal coronary arteries. However, with the exception that exercise elicited angina and electrocardiographic changes more consistently in the group with coronary artery disease, there were no significant differences between the two groups.

Predictors of long-term mortality in Multicenter Automatic Defibrillator Implantation Trial II (MADIT II) patients with implantable cardioverter-defibrillators.

BACKGROUND Data on long-term follow-up and factors influencing mortality in implantable cardioverter-defibrillator (ICD) recipients are limited. OBJECTIVE The aim of this study was to evaluate mortality during long-term follow-up and the predictive value of several risk markers in the Multicenter Automatic Defibrillator Implantation Trial II (MADIT II) patients with implanted cardioverter-defibrillators (ICDs). METHODS The study involved U.S. patients from the MADIT II trial randomized to and receiving ICD treatment. Data regarding long-term mortality were retrieved from the National Death Registry. Several clinical, biochemical, and electrocardiogram variables were tested in a multivariate Cox model for predicting long-term mortality, and a score identifying high-, medium-, and lower risk patients was developed. RESULTS The study population consisted of 655 patients, mean age 64 +/- 10 years. During a follow-up of up to 9 years, averaging 63 months, 294 deaths occurred. The 6-year cumulative probability of death was 40%, with evidence of a constant risk of about 8.5% per year among survivors. Median survival was estimated at 8 years. Multivariate analysis identified age >65 years, New York Heart Association class 3-4, diabetes, non-sinus rhythm, and increased levels of blood urea nitrogen as independent risk predictors of mortality. Patients with three or more of these risk factors were characterized by a 6-year mortality rate of 68%, compared with 43% in those with one to two risk factors and 19% in patients with no risk factors. CONCLUSION A combination of a few readily available clinical variables indicating advanced disease and comorbid conditions identifies ICD patients at high risk of mortality during long-term follow-up.

The prognostic significance of first myocardial infarction type (Q wave versus non-Q wave) and Q wave location

The prognostic significance of the type of first acute myocardial infarction (Q wave versus non-Q wave) and Q wave location (anterior versus inferoposterior) was determined from a multicenter data base involving 777 placebo-treated patients who were participants in the Multicenter Diltiazem Post-Infarction Trial. There were 224 patients (29%) with a non-Q wave infarction, 326 (42%) with an inferoposterior Q wave infarction and 227 (29%) with an anterior Q wave infarction. Mean left ventricular ejection fraction was significantly (p less than 0.001) lower in patients with an anterior Q wave infarction than in the other two groups (anterior Q wave 0.39; inferior Q wave 0.52; non-Q wave 0.53). Nevertheless, the total cardiac mortality rate during the follow-up period (average 25 months per patient) was only marginally higher (p = 0.42) in the anterior Q wave group (8.4%) than in the other two groups (inferoposterior Q wave 7.1%; non-Q wave 6.3%). The total first recurrent cardiac event was somewhat higher (p = 0.08) in the anterior Q wave group (18.1%) than in the other two groups (inferoposterior Q wave 11.7%; non-Q wave 15.6%). Survivorship analyses extending over 3 years revealed that electrocardiographic classification of the type of first infarction and Q wave location did not make significant independent contributions to the risk of postinfarction cardiac death or first recurrent cardiac event, either before or after adjustment for baseline clinical variables.

Acute pulmonary edema due to ischemic heart disease without accompanying myocardial infarction: Natural history and clinical profile

The natural history of acute cardiogenic pulmonary edema was studied in a group of patients who did not have acute myocardial infarction, cardiomyopathy, or valvular heart disease. Most of these patients had coronary artery disease. Cardiac catheterization in selected patients showed depressed contractility in some with segmental abnormalities. In the group older than 70 years, this carried a 70 percent two-year mortality rate. It is important to approach patients with this syndrome vigorously, both diagnostically and therapeutically. Acute, reversible segmental ischemia may be responsible for this syndrome and may respond to measures designed to prevent recurrent ischemia.

A new electrocardiographic classification for post-myocardial infarction clinical trials

Abstract A new electrocardiographic code was developed for clinical trials involving patients with acute myocardial infarction (AMI). In the Multicenter Post-Infarction Program (MPIP), the electrocardiogram, classified by the Minnesota code, was not useful as a clinical predictor and played almost no role in subsequent analysis. To test its value the new code was applied to the electrocardiograms of 653 of the 866 patients in the MPIP data base who had sustained a first AMI. The MPIP code identifies AMI by region and severity. The 4 regions are anterior, lateral, inferior and posterior, defined by traditional criteria. Severity codes include Q-wave and non-Q-wave AMI, ST depression and no ischemic changes. The interpretation for each of 4 regions results in a 4-digit location severity code that is amenable to sorting and analysis. Fourteen separate and mutually exclusive groups were identified. Mortality gradients were found within the inferior AMI groups, but not within the anterior AMI groups. Mean ejection fraction was 50% for patients with isolated anterior infarction and decreased progressively (p

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

Prognosis and response to therapy of first inpatient and outpatient heart failure event in a heart failure clinical trial: MADIT‐CRT

Hospitalization for worsening heart failure (HF) is known to increase mortality and morbidity risk and has been frequently used as an endpoint in randomized clinical trials. Whether outpatient management of HF exacerbation carries similar prognostic and therapeutic information is less well known, but could be important for the design of trials that use HF hospitalization as an endpoint.