Coronary thrombosis has been reported to occur most frequently in lipid-rich plaques with rupture of a thin fibrous cap and contact of the thrombus with a pool of extracellular lipid. However, the frequency of coronary artery thrombosis with or without fibrous cap rupture in sudden coronary death is unknown. In this study, we compared the incidence and morphological characteristics of coronary thrombosis associated with plaque rupture versus thrombosis in eroded plaques without rupture.

Improved outcome of heart failure in response to medical therapy, coupled with a critical shortage of donor organs, makes it imperative to restrict heart transplantation to patients who are most disabled by heart failure and who are likely to derive the maximum benefit from transplantation. Hemodynamic and functional indexes of prognosis are helpful in identifying these patients. Stratification of ambulatory heart failure patients by objective criteria, such as peak exercise oxygen consumption, has improved ability to select appropriate adult patients for heart transplantation. Such patients will have a poor prognosis despite optimal medical therapy. When determining the impact of individual comorbid conditions on a patient's candidacy for heart transplantation, the detrimental effects of each condition on posttransplantation outcome should be weighed. Evaluation of patients with severe heart failure should be done by a multidisciplinary team that is expert in management of heart failure, performance of cardiac surgery in patients with low left ventricular ejection fraction, and transplantation. Potential heart transplant candidates should be reevaluated on a regular basis to assess continued need for transplantation. Long-term management of heart failure should include continuity of care by an experienced physician, optimal dosing in conventional therapy, and periodic reevaluation of left ventricular function and exercise capacity. The outcome of high-risk conventional cardiovascular surgery should be weighed against that of transplantation in patients with ischemic and valvular heart disease. Establishment of regional specialized heart failure centers may improve access to optimal medical therapy and new promising medical and surgical treatments for these patients as well as stimulate investigative efforts to accelerate progress in this critical area.

The epidemiological approach to investigation of cardiovascular disease was innovated in 1948 by Ancel Keys' Seven Countries Study and T.R. Dawber's Framingham Heart Study. Conducted in representative samples of the general population, these investigations provided an undistorted perception of the clinical spectrum of cardiovascular disease, its incidence and prognosis, the lifestyles and personal attributes that predispose to cardiovascular disease, and clues to pathogenesis. The many insights gained corrected numerous widely held misconceptions derived from clinical studies. It was learned, for example, that the adverse consequences of hypertension do not derive chiefly from the diastolic pressure, left ventricular hypertrophy was not an incidental compensatory phenomenon, and small amounts of proteinuria were more than orthostatic trivia. Exercise was considered dangerous for cardiovascular disease candidates; smoking, cholesterol, and a fatty diet were regarded as questionable promoters of atherosclerosis. The entities of sudden death and unrecognized myocardial infarction were not widely appreciated as prominent features of coronary disease, and the disabling and lethal nature of cardiac failure and atrial fibrillation was underestimated. It took epidemiological research to coin the term "risk factor" and dispel the notion that cardiovascular disease must have a single origin. Epidemiological investigation provided health professionals with multifactorial risk profiles to more efficiently target candidates for cardiovascular disease for preventive measures. Clinicians now look to epidemiological research to provide definitive information about possible predisposing factors for cardiovascular disease and preventive measures that are justified. As a result, clinicians are less inclined to regard usual or average values as acceptable and are more inclined to regard optimal values as "normal." Cardiovascular events are coming to be regarded as a medical failure rather than the first indication of treatment.

The first successful surgical repair of coarctation of the aorta (CoAo) was performed in 1944, but during the years that followed a high incidence of recoarctation was seen, ranging from 20% to 86%. In response to that problem, the patch aortoplasty was introduced in 1957; however, true aneurysms were found in the aortic wall opposite the patch after Dacron patch aortoplasty, particularly when the coarctation ridge was excised. The purpose of our review was to evaluate the results of patch aortoplasty for CoAo using a relatively new material, polytetrafluoroethylene (PTFE), and an operative technique that does not involve resection of the coarctation ridge.

The cardiovascular applications of nuclear magnetic resonance (MR) techniques in coronary artery disease have increased considerably in recent years. Technical advantages of MR imaging in comparison with other techniques are the excellent spatial resolution, the characterization of myocardial tissue, and the potential for three-dimensional imaging. This allows the accurate assessment of left ventricular mass and volume, the differentiation of infarcted tissue from normal myocardial tissue, and the determination of systolic wall thickening and regional wall motion abnormalities. Myocardial perfusion, metabolism, and inducible myocardial ischemia with the use of pharmacological stress also can be assessed by MR techniques. Future technical improvements in real-time imaging and development of noninvasive visualization of the coronary arteries and coronary artery bypasses will constitute a tremendous progress in clinical cardiology. Early detection and flow assessment of stenosed coronary arteries by MR angiography with the use of flow velocity measurements may outweigh the cost inherent to the MR imaging procedure. A particular strength of the MR technique is the potential to encompass cardiac anatomy, perfusion, function, metabolism, and coronary angiography in a single test. The replacement of multiple diagnostic tests with one MR test may have major effects on cardiovascular healthcare economics.

Nearly 40 years after its invention, the angiogram is still considered by most physicians to be the "gold standard" for defining coronary anatomy. Careful investigations have revealed many deficiencies inherent in this approach. The purpose of this article is to outline the evidence that our current preoccupation with coronary "luminology" may be misguided and to propose a rational paradigm for future practice and investigation. Angiography depicts coronary anatomy from a planar two-dimensional silhouette of the lumen. Angiography is limited in resolution to four or five line pairs per millimeter. Confounding factors include vessel tortuosity, overlap of structures, and the effects of lumen shape. After intervention, a hazy, broadened silhouette may overestimate the actual gain in lumen size. Studies show marked disparity between the apparent severity of lesions and their physiological effects. After myocardial infarction, cardiologists too often do not make an attempt to demonstrate the physiological significance of the stenosis before performing percutaneous coronary revascularization. Similarly, the allure of a better, more gratifying angiogram with new interventional devices appears to be a dominant factor in their popularity. Interventional cardiologists should be aware that techniques yielding marked angiographic benefit may also generate important but unrecognized hazards. The dissociation between the angiogram and clinical outcome should influence future research efforts. Our review of the literature indicates that we may benefit from shifting the current focus and preoccupation with coronary luminology to achieving the desired clinical end point: promoting survival and long-term freedom from myocardial infarction and the disabling symptoms of coronary heart disease.

This article briefly reviews recent experimental studies which show that beta-adrenergic receptor stimulation produces an important enhancement of the force-frequency relation on myocardial contractility. The basic property of the force-frequency effect to progressively enhance myocardial contractility as heart rate increases is augmented at each level of increasing adrenergic stimulation. This newly described intrinsic mechanism for the control of cardiac inotropic state, graded beta-adrenergic amplification of the force-frequency relation, is strongly manifested during normal exercise and infusion of a beta-adrenergic agonist at rest, and it influences both systolic and diastolic ventricular function. Significant impairment of adrenergic amplification of the force-frequency relation is observed in experimental heart failure and could contribute to impaired cardiac function during stress or exercise in this setting.

Mediastinitis is a severe complication of coronary artery bypass graft surgery (CABG). The purpose of the present study was to determine preoperative and intraoperative variables that predict mediastinitis and to determine the impact of this complication on long-term survival.

This consensus document is an attempt to provide an organized method of reporting pediatric ALS data in out-of-hospital, emergency department, and in-hospital settings. For this methodology to gain wide acceptance, the task force encourages development of a common data set for both adult and pediatric ALS interventions. In addition, every effort should be made to ensure that consistent definitions are used in all age groups. As health care changes, we will all be challenged to document the effectiveness of what we currently do and show how new interventions or methods of treatment improve outcome and/or reduce cost. Only through collaborative research will we obtain the necessary data. For these reasons, and to improve the quality of care and patient outcomes, it is the hope of the task force that clinical researchers will follow the recommendations in this document. It is recognized that further refinements of this statement will be needed; these recommendations will improve only when researchers, clinicians, and EMS personnel use them, work with them, and modify them. Suggestions, emendations, and other comments aimed at improving the reporting of pediatric resuscitation should be sent to Arno Zaritsky, MD, Eastern Virginia Medical School, Children's Hospital of the King's Daughter, Division of Critical Care Medicine, 601 Children's Lane, Norfolk, VA 23507.

The high affinity of even relatively short sequences of DNA for their target mRNA suggests that antisense agents represent an ideal method of suppressing specific gene products both in vitro and in vivo. In experiments performed thus far, an effect on the target mRNA in cultured vascular cells and in the vessel wall can be documented. The in vitro activity, toxicity, and pharmacokinetic data of antisense oligonucleotides are encouraging, and the in vivo animal experiments demonstrating suppression of neointimal formation are very promising. If animals trials presently under way show continued suppression not only of intimal formation but also of loss of lumen caliber after a single application, then effective delivery of antisense oligonucleotides is a realistic possibility. Nevertheless, some words of caution regarding the use of antisense oligonucleotides are warranted. Potential nonspecific effects of antisense oligonucleotides should be carefully considered in studies in which antisense agents are used to define biological functions of specific genes. In particular, demonstration that the target mRNA has been suppressed does not prove that other sequences within the mRNA pool have not also been suppressed. Critical control measures include adding back the target mRNA or protein and demonstrating similar biological effects with antisense sequences, which also suppress target gene expression directed at different regions of the target mRNA. At the clinical level, the systemic effects of antisense oligonucleotides, the dosage required, the timing of administration compared with mechanical intervention, and the toxicity of breakdown products all need to be established. In addition, the most appropriate targets for antisense use in restenosis remain largely obscure. Indiscriminate suppression of cell-cycle genes or proto-oncogenes may be as acutely toxic as current anticancer chemotherapy if the site delivery is not completely localized. Furthermore, much of the clinical evidence suggests that restenosis is a chronic process, continuing to develop weeks to months after the procedure. If this is the case, then the current approaches that rely on a transient, local application of an antisense agent may fail. If, however, a target gene is identified that is specific to vascular tissue, then repeated administration of an antisense agent may be tolerated via a systemic route. This approach has proved successful in targeting mutated genes with little suppression of closely related genes and with minimal systemic toxicity. An alternative approach is to transfect the target tissue with a gene that makes it susceptible to systemic delivery of a drug that is not normally toxic to mammalian cells.(ABSTRACT TRUNCATED AT 400 WORDS)