Although thrombolytic therapy reduces long-term mortality in acute myocardial infarction, many clinicians remain concerned about an increased risk of ventricular arrhythmias associated with the use of these agents.

In contrast with current standard regimens, it seems more appropriate to tailor thrombolytic therapy to individual patient characteristics. A proposed model for such tailored therapy is based on individual assessment of benefits and risks of thrombolytic therapy, taking into account the response of individual patients to the therapy given.

The increased incidence and prevalence of congestive heart failure place a high priority on novel treatment strategies. Left ventricular ejection fraction remains the single most valuable measurement providing both diagnostic and prognostic insights. The most systematic approach to heart failure involves an objective assessment of functional disability, to include exercise tests such as a 6-minute walk under standardized conditions. Left ventricular dysfunction incites a host of neurohumoral compensations that are of fundamental importance in the heart failure syndrome expression. Both vasoconstrictor and vasodilator neurohormones are stimulated and provide new therapeutic opportunities. The therapeutic approach to heart failure begins with a strong emphasis on prevention, patient education, and self-participation in therapy with respect to both its monitoring and adjustment. Diuretics remain a mainstay of therapy but, in the face of severe heart failure, may become ineffectual, requiring constant infusion of loop-active diuretics, combination diuretics, or diuretics in association with concomitant low-dose dopamine infusion. Vasodilator therapy has been an important advance: combination hydralazine and nitrate therapy was initially shown to be efficacious in improving survival, and more recently, angiotensin-converting enzyme (ACE) inhibitors, in the form of enalapril, have shown incremental benefit on survival over this combination. Interestingly, there is now evidence from both SOLVD and SAVE to demonstrate an unexpected and, as yet, unexplained reduction in the frequency of both unstable angina and myocardial infarction. Although, on balance, the weight of evidence concerning the long-term efficacy of inotropic agents has been disappointing, especially as it relates to their unfavorable effects on survival, recent information on vesnarinone, an agent with a complex and diversified mechanism of action, suggests that with appropriate doses, improved symptoms and survival are possible. A substantial amount of new information from randomized placebo-controlled trials attests to the symptomatic relief, hemodynamic improvement, and gain in exercise performance achieved by digoxin. A long-term survival study is ongoing to assess its effects on mortality. beta-Blockers, especially metoprolol, appear beneficial in some patients with heart failure, possibly related to their reduction in sympathetic nervous activity and restoration of beta-receptor population, with resultant improved contractile performance, enhanced myocardial relaxation, and overall increase in cardiac efficiency. Based on available evidence, the best contemporary approach to treatment involves the use of ACE inhibitors coupled with diuretic therapy, either continuous or intermittent, to relieve central or peripheral congestion. The addition of digoxin or a hydralazine nitrate combination is a logical next step, with commencement of low-dose beta-blocker a reasonable option.(ABSTRACT TRUNCATED AT 400 WORDS)

Postextrasystolic potentiation (PESP), the increase in contractility that follows an extrasystole, is an interesting phenomenon that has been known for almost 100 years. The literature on this effect is reviewed. It is found that there is significant evidence that the phenomenon is independent of muscle loading and represents a distinct property of the myocardium. Examination of the literature pertaining to the cause of the effect suggests that calcium shifts within the sarcoplasmic reticulum are responsible, although there are some conflicts with this conclusion. Regarding the utility of PESP as a diagnostic test of latent viability of ischemic myocardium, the literature review reveals contradictions and conflicts with several methodological problems of the experiments. Finally, concerning the utility of continuous PESP (paired-pacing) to augment ventricular function in the failing ventricle, the studies again are inconclusive and methodologically suspect. Conditions for the proper analysis of the PESP response are reported, and suggestions for future studies are introduced.

Despite recent declines in mortality, cardiovascular diseases are the leading cause of death in the United States today. It appears that many of the major risk factors for coronary disease have been identified. Researchers are still learning about different modifiable factors that may influence cardiovascular diseases. Socioeconomic status may provide a new focus. The principal measures of SES have been education, occupation, and income or combinations of these. Education has been the most frequent measure because it does not usually change (as occupation or income might) after young adulthood, information about education can be obtained easily, and it is unlikely that poor health in adulthood influences level of education. However, other measures of SES have merit, and the most informative strategy would incorporate multiple indicators of SES. A variety of psychosocial measures--for example, certain aspects of occupational status--may be important mediators of SES and disease. The hypothesis that high job strain may adversely affect health status has a rational basis and is supported by evidence from a limited number of studies. There is a considerable body of evidence for a relation between socioeconomic factors and all-cause mortality. These findings have been replicated repeatedly for 80 years across measures of socioeconomic level and in geographically diverse populations. During 40 years of study there has been a consistent inverse relation between cardiovascular disease, primarily coronary heart disease, and many of the indicators of SES. Evidence for this relation has been derived from prevalence, prospective, and retrospective cohort studies. Of particular importance to the hypothesis that SES is a risk factor for cardiovascular disease was the finding by several investigators that the patterns of association of SES with coronary disease had changed in men during the past 30 to 40 years and that SES has been associated with the decline of coronary mortality since the mid-1960s. However, the declines in coronary mortality of the last few decades have not affected all segments of society equally. There is some evidence that areas with the poorest socioenvironmental conditions experience later onset in the decline in cardiovascular mortality. A number of studies suggest that poor living conditions in childhood and adolescence contribute to increased risk of arteriosclerosis. Some of these studies have been criticized because of their nature, and others for inadequate control of confounding factors.(ABSTRACT TRUNCATED AT 400 WORDS)

Conventional risk factors (especially high arterial pressure, elevated cholesterol and glucose levels, and cigarette smoking) are useful predictors of morbid atherosclerotic and hypertensive events, and their control variably reduces the incidence of events. However, both the ability to predict risk and the ability to reduce it by modification of established risk factors are limited. These limitations occur in part because the progression from risk factor exposure to morbid events depends on the variable likelihood that individuals exposed to the same risk factors will progress through two stages: the development of asymptomatic or "preclinical" anatomic and functional cardiovascular disease in response to standard risk factors and other variables, and the precipitation of morbid events by progression of preclinical disease or by the action of additional "triggering" mechanisms in the presence of preclinical disease. Advances in diagnostic methodology now make possible accurate noninvasive detection in many asymptomatic individuals of preclinical disease such as left ventricular hypertrophy, carotid atherosclerosis, and renal dysfunction. Progress in elucidating stimuli to left ventricular hypertrophy and systemic atherosclerosis suggests that focusing research separately on these two stages of disease evolution is a fruitful strategy. The closer relation of measures of preclinical disease than risk factors with the subsequent risk of complications indicates that their detection improves clinical risk stratification. However, critical testing of whether clinical outcome is improved or treatment cost is lowered by basing antihypertensive or antihyperlipidemic treatment decisions in part on the presence of preclinical cardiovascular disease is needed before this strategy is adopted on a widespread scale.

The workshop provided the opportunity to discuss issues and develop and integrate ideas. The following recommendations for public policies, education programs, and high-priority research initiatives were developed: Recommendations for Public Policies: Focus on prevention by requiring school programs to emphasize appropriate diet, physical activity, and general health guidance to promote cardiovascular health and prevent disease through federal funding. Provide better access to exercise (city planning, work-site interventions). Influence food availability and accessibility. Influence reimbursement policies for effective early intervention and prevention strategies for obesity. Reevaluate policies for use of drugs in the treatment of obesity. Recommendations for Education Programs: Sponsor scientific workshop to: Define the most appropriate weight standards for prevention and treatment. Identify who should lose weight and why, when, and how. Promote the fact that obesity is an important health risk factor, even at moderate levels, and that excess visceral fat is particularly hazardous. Target health care professionals, consumers, and the media for education about: Nature of obesity as a heterogeneous syndrome. Recommendations for diet, exercise, behavioral interventions, drugs, and surgery. Recognition of special needs of populations of different ethnicity, gender, age, etc. State-of-the-art treatment and treatment programs. High-Priority Research Initiatives: Build better bridges between basic research and treatment/prevention practices. Acknowledge that obesity is a heterogeneous syndrome that may best be characterized as different obesities. Research on defining subtypes. Implications for etiology and treatment. Better characterization of genotypes and phenotypes. Study the effects of weight loss, weight gain,and weight cycling on medical and psychosocial outcomes and mortality.(ABSTRACT TRUNCATED AT 250 WORDS)