We reviewed the records of 26 infants with congenital junctional ectopic tachycardia (JET) from seven institutions to examine the evolution in the management of this tachycardia that is difficult to treat. JET was defined electrocardiographically as an incessant tachycardia with normal QRS morphology and atrioventricular (AV) dissociation. The ventricular rate ranged from 140 to 370 beats/min (mean, 230 beats/min); 16 of 26 patients had cardiac failure. Treatment success was defined as a stable decrease in the rate of JET, below 150 beats/min; partial success was a significant decrease of JET rate with alleviation of symptoms. All patients received digoxin with no significant effect. Propranolol was given to 16 patients, with two successes and one partial success. Combinations of other conventional agents were used in 11 patients with two successes; 14 patients were treated with amiodarone, which resulted in eight successes and three partial successes; three patients died suddenly on medical treatment (amiodarone, one patient; propranolol, one patient; or amiodarone plus propranolol, one patient); sudden AV block was a possible cause and consequently, two later patients had pacemaker implantation as well as medical treatment. His catheter ablation was successfully performed twice but contributed to death in a newborn; three surgical His ablations were performed for intractable JET with two successes and one death. The overall mortality was 35%. Among survivors, treatment has been stopped without any complications in five patients ranging in age from 10 months to 8 years (mean, 3.5 years). It seems that amiodarone alone is the best drug for treatment of congenital JET; necessity for permanent pacing remains unsettled. His ablation should be reserved only for intractable JET.

An acute myocardial infarction, particularly one that is large and transmural, can produce alterations in the topography of both the infarcted and noninfarcted regions of the ventricle. This remodeling can importantly affect the function of the ventricle and the prognosis for survival. In the early period, infarct expansion has been recognized by echocardiography as a lengthening of the noncontractile region. The noninfarcted region also undergoes an important lengthening that is consistent with a secondary volume-overload hypertrophy and that can be progressive. The extent of ventricular enlargement after infarction is related to the magnitude of the initial damage to the myocardium and, although an increase in cavity size tends to restore stroke volume despite a persistently depressed ejection fraction, ventricular dilation has been associated with a reduction in survival. The process of ventricular enlargement can be influenced by three interdependent factors, that is, infarct size, infarct healing, and ventricular wall stresses. A most effective way to prevent or minimize the increase in ventricular size after infarction and the consequent adverse effect on prognosis is to limit the initial insult. Acute reperfusion therapy has been consistently shown to result in a reduction in ventricular volume. The reestablishment of blood flow to the infarcted region, even beyond the time frame for myocyte salvage, has beneficial effects in attenuating ventricular enlargement. The process of scarification can be interfered with during the acute infarct period by the administration of glucocorticosteroids and nonsteroidal antiinflammatory agents, which result in thinner infarcts and greater degrees of infarct expansion. Modification of distending or deforming forces can importantly influence ventricular enlargement. Even short-term augmentations in afterload have deleterious long-term effects on ventricular topography. Conversely, judicious use of nitroglycerin seems to be associated with an attenuation of infarct expansion and long-term improvement in clinical outcome. Long-term therapy with an angiotensin converting enzyme inhibitor can favorably alter the loading conditions on the left ventricle and reduce progressive ventricular enlargement as demonstrated in both experimental and clinical studies. With the former therapy, this attenuation of ventricular enlargement was associated with a prolongation in survival. The long-term clinical consequences of long-term angiotensin converting enzyme inhibitor therapy after myocardial infarction is currently being evaluated. Although studies directed at attenuating left ventricular remodeling after infarction are in the early stages, it does seem that this will be an important area in which future research might improve long-term outcome after infarction.

The efficacy of percutaneous transluminal coronary angioplasty (PTCA) in relieving symptoms of coronary artery disease is well established, and the technique has become widely used in patients with multivessel as well as single-vessel disease. The technique has only recently been widely applied, and long-term outcome is, therefore, not well defined. Studies of patients who underwent the procedure early in its development were primarily of patients with single-vessel disease. These studies demonstrated low mortality (1%/yr) and nonfatal myocardial infarction (MI) rates (1-3%/yr), with a majority of patients (85-90%) clinically improved after 5 years. More recent studies of patients with multivessel disease demonstrate higher mortality (2-4%/yr) and a similar incidence of nonfatal MI (2-3%/yr), with improvement in symptoms in the majority (70-80%). The degree of revascularization can be an important factor in symptomatic improvement as well as in the need for subsequent revascularization. A favorable outcome is most likely when all lesions attempted with PTCA are reduced by at least 20% and no significant residual lesions remain in any proximal vessels. The efficacy of PTCA as compared with bypass surgery in patients with multivessel disease is uncertain. The results of several large ongoing and planned clinical trials should provide the information necessary to more fully understand the use of angioplasty in this setting. Although no study has directly compared PTCA with coronary artery bypass surgery, nonrandomized comparisons indicate similar long-term outcomes.(ABSTRACT TRUNCATED AT 250 WORDS)

Recent advances in thrombolytic therapy and balloon angioplasty have resulted in reperfusion therapy as a logical maneuver in the treatment of evolving myocardial infarction. The introduction of electrolytes, oxygen, and cellular elements, especially neutrophils, however, into the previously ischemic bed may initiate cellular and biochemical changes that limit the amount of potentially salvageable myocardium (reperfusion injury). Experimental studies have demonstrated that microvascular damage may play an important role in the pathogenesis of this phenomenon. Reperfusion enhances the infiltration of activated neutrophils into the ischemic bed, and neutrophil plugging of capillary lumens in association with extensive disruption of endothelial cells results in a progressive decrease in blood flow (the "no-reflow" phenomenon). Activated neutrophils may potentiate the inflammatory response, produce cellular damage, and reduce capillary blood flow by producing chemoattractants, proteolytic enzymes and reactive oxygen species, and arachidonate products, respectively. Therapeutic strategies that modify the interaction between neutrophils and endothelium have shown promising results in experimental preparations for reperfusion. The administration of both perfluorochemical (Fluosol, Alpha Therapeutic Corp., Los Angeles, California) and adenosine after reperfusion has resulted in enhanced myocardial salvage after 90 minutes of ischemia in the canine model. Histological studies have shown reduced neutrophil infiltration and relative preservation of endothelial cells without neutrophil plugging with both agents. Both adenosine and perfluorochemical have been shown to reduce neutrophil adherence and cytotoxicity to endothelial cell cultures. These findings suggest that suppression of neutrophil activation, especially chemotaxis, might be an ideal step to reduce this component from the inflammatory response in the ischemic myocardium after reperfusion. Clinical trials seem warranted to determine the role of reperfusion injury in limiting myocardial salvage in patients undergoing reperfusion within the first few hours of a thrombotic event.

Regional myocardial ischemic injury progresses as a "wave-front" phenomenon from the endocardium to the epicardium. Myocyte damage can be reversible or irreversible and is dependent on the duration of ischemia. Endothelial cell injury lags behind myocyte injury. Reperfusion of ischemic myocardium can result in the acceleration of endothelial injury with resultant conversion of surrounding reversibly injured myocytes to irreversible damage; this has been termed the "no-reflow" phenomenon. This process can be accelerated by the presence of neutrophils. Agents such as perfluorochemicals and adenosine, which attenuate endothelial injury and inhibit neutrophil infiltration, also reduce infarct size in animal models. Infarct size reduction with perfluorochemical was observed with both intracoronary and intravenous infusion. Infarct healing was not adversely affected except for the persistence of perfluorochemical-laden macrophages. These studies suggest that perfluorochemicals and adenosine might be beneficial adjuvants to thrombolytic therapy in the reduction of reperfusion injury.

Results of multiple studies have amply verified the benefit of urgent coronary revascularization for patients who have acute myocardial infarction (MI). Currently, intravenous thrombolytic therapy is the treatment of choice for many patients, especially those 75 years old or younger who present within 6 hours of symptom onset and who are without contraindications to thrombolytic therapy. Some patients treated within 6-24 hours of symptom onset may also benefit, but this remains unproven. The thrombolytic agents currently in use or being extensively evaluated include streptokinase, urokinase, tissue-type plasminogen activator (t-PA), anisoylated plasminogen streptokinase activator complex (APSAC or anistreplase), and single-chain urokinase-type plasminogen activator (scu-PA). The agent t-PA has the potential advantage of being clot selective and, thereby, relatively fibrinogen sparing, and its efficacy in terms of restoration of vessel patency is less dependent on the time of administration as compared with that of streptokinase and urokinase. It is not yet known whether this will translate into improved patient survival as compared with that achieved by the less-expensive agents streptokinase and APSAC. Treatment regimens of combination thrombolytic agents have been developed, but the optimal combinations have not yet been determined. Patients who are in cardiogenic shock and those in whom thrombolytic therapy is contraindicated can probably benefit from angioplasty or bypass surgery. Results of several studies have suggested that immediate angioplasty after successful thrombolysis is not beneficial; however, the potential benefit of angioplasty or bypass surgery for failed thrombolytic therapy is yet to be evaluated. Although many advances have been made, further research is clearly needed in the area of reperfusion.

Restenosis after percutaneous transluminal coronary angioplasty (PTCA) probably results from pathophysiological mechanisms that are initiated during PTCA. Platelet deposition or exposed subendothelial connective tissue initiates complex blood element and vessel wall interactions that are not completely understood and leads to a proliferative response at the site of injury. The incidence of restenosis is also related to clinical, anatomic, and procedural variables. An increased frequency of restenosis is seen in patients who have recent onset of angina, unstable angina, or vasospastic angina, and in those who have diabetes. Stenoses in the proximal left anterior descending coronary artery, the ostium of the right coronary artery, and the proximal portion of a bypass vein graft have higher rates of restenosis than lesions at other sites. Restenosis can be predicted by an incomplete PTCA, which is identified by a high residual pressure gradient across the stenosis. Mechanical and pharmacological methods of preventing restenosis are under investigation. Intravascular stenting with expandable metal sleeves and laser angioplasty have shown encouraging results. Longer balloon inflation time can help prevent early elastic recoil. Platelet inhibitors (e.g., aspirin, dipyridamole, and sulfinpyrazone) do not appear to have an effect on restenosis. Agents, however, that interfere with platelet deposition at the PTCA site and that modify the effect of platelet-derived growth factor and medial cell proliferation show promise for control of restenosis.

The advent of balloon angioplasty as a clinical device crystallized the concept of nonsurgical revascularization. The problems of restenosis, diffuse disease, and total occlusions persist despite the demonstrated efficacy of balloon angioplasty. During the past 5 years, a variety of laser devices and catheter designs have demonstrated usefulness in the treatment of peripheral vascular disease. Initial success rates of 70-90% have been reported in occluded femoropopliteal arteries. Further clinical trials are warranted to compare the relative efficacy of these devices with each other and conventional therapies. Thermal ablative devices have not yet shown great promise for treatment of coronary disease. Modified versions of these devices as well as nonthermally acting excimer lasers are promising as clinical tools for enhancing our ability to nonsurgically revascularize patients, and trials with these devices are now underway.

Silent myocardial ischemia is now recognized as a common manifestation within the clinical spectrum of coronary artery disease and has important physiological, hemodynamic, and prognostic implications. Asymptomatic ST segment shifts during ambulatory 24-hour electrocardiographic monitoring and exercise treadmill testing are far more frequent than symptomatic ST shifts and are associated with abnormal myocardial perfusion as assessed by radionuclide scintigraphy. Seemingly healthy asymptomatic patients and patients with stable coronary artery disease, unstable angina, or recent myocardial infarction are all at higher risk of subsequent cardiovascular morbidity if there is evidence of silent ischemia. Hemodynamic studies have clearly documented the adverse effects of ischemia on left ventricular systolic function. Furthermore, diastolic relaxation and filling appear to be altered by both symptomatic and asymptomatic ischemia during atrial pacing and dynamic exercise independent of changes in systolic function. The majority of patients with coronary artery disease have abnormal diastolic parameters at rest, regardless of anginal symptoms, which are partially reversible after coronary revascularization procedures such as angioplasty and bypass surgery. Regional diastolic dysfunction from scar or ischemia can lead to asynchronous myocardial relaxation and thus affect global diastolic function, depending on the extent and severity of the regional abnormalities. Diastolic function seems more susceptible to ischemia than systolic function and can take longer to recover.(ABSTRACT TRUNCATED AT 250 WORDS)

The sympathetic nervous system becomes activated in heart failure, and while this is initially beneficial, the consequences of prolonged raised levels of catecholamines can be counterproductive. Xamoterol, a partial agonist that acts on the cardiac beta 1-adrenergic receptor, modifies the response of the heart to variations in sympathetic activity. At rest, it produces modest improvements in cardiac contractility, relaxation, and filling without increase in myocardial oxygen demand. The improvements are maintained during exercise although the attendant tachycardia is attenuated. The beneficial effects of xamoterol on both systolic and diastolic function suggested that it would be effective in patients with mild-to-moderate heart failure, and this was demonstrated in small placebo-controlled studies where effort tolerance and symptoms were improved. A large multicenter study program comprised of four studies demonstrated that patients with mild-to-moderate heart failure randomized to xamoterol (n = 617) 200 mg b.i.d. for 3 months significantly (p less than 0.0001) improved exercise capacity by 37% as compared with the placebo group (n = 300) with an increase of 18%. The xamoterol group also showed significant improvements in symptoms of breathlessness, fatigue, and life values as compared with the placebo group. In one of the multicenter studies in which 433 patients were randomized to xamoterol (n = 220), placebo (n = 109), and a positive control, digoxin 0.125 mg b.i.d. (n = 104), the percentages of improvement in exercise work were 33%, 5%, and 17%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Most research in the field of chronic heart failure during the last 20 years has been directed toward defining and understanding the abnormalities of systolic function seen in this disorder, but systolic performance is not a determinant of effort tolerance. Several lines of evidence, however, suggest a strong relation between exercise capacity and abnormalities of diastolic function in chronic heart failure. Of all the commonly measured hemodynamic variables, effort tolerance (whether limited by dyspnea or fatigue) varies more closely with the level of left ventricular filling pressure than the left ventricular ejection fraction. Consequently, drugs that lower ventricular filling pressures are more likely to enhance exercise capacity than drugs that primarily increase cardiac output and left ventricular ejection phase indexes. Vasodilator drugs do not reduce left ventricular filling pressure, however, by simply redistributing central blood volume to the peripheral capacitance circuits because these agents do not predictably decrease left ventricular volumes. Instead, clinically effective drugs seem to reduce left ventricular filling pressure primarily by producing a favorable shift in the left ventricular diastolic pressure-volume relation. Conversely, agents that adversely affect the diastolic pressure-volume relation frequently cause clinical deterioration. These findings suggest that abnormalities of diastolic rather than systolic performance may be the most important determinants of the clinical status and exercise intolerance of patients with chronic heart failure.